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A Prospective Evaluation of Natriuretic Peptide Based Referral of CHF Patients in Primary Care (PREFER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02807857
Recruitment Status : Completed
First Posted : June 21, 2016
Results First Posted : January 5, 2021
Last Update Posted : February 24, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Chronic Heart Failure (CHF)
Intervention Procedure: Standard care
Enrollment 1415
Recruitment Details The enrolled set consisted of 1415 patients. 861 patients were referred to a cardiologist within this study and Based on findings from the interim-analysis, Novartis decided to terminate the study prematurely in March 2018.
Pre-assignment Details  
Arm/Group Title Enrolled Patients
Hide Arm/Group Description Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe. Patients who were considered clinically stable with NT-proBNP levels > 600 pg/ml were described and analyzed in the Follow-Up set.
Period Title: Enrolled Set
Started 1415
Completed 864
Not Completed 551
Reason Not Completed
Patients not suitable for follow-up.             551
Period Title: Follow-Up Set
Started 864
Completed 680
Not Completed 184
Reason Not Completed
Study Terminated By Sponsor             131
Withdrawal by Subject             8
Lost to Follow-up             7
Physician Decision             6
Adverse Event             3
Death             27
Relocation             2
Arm/Group Title Enrolled Patients
Hide Arm/Group Description Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe. Patients who were considered clinically stable an with NT-proBNP levels > 600 pg/ml were referred to a cardiologist for evaluation and were in the follow-up set.
Overall Number of Baseline Participants 1415
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1415 participants
69.8  (11.6)
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 1415 participants
<65 years 482
≥65 years to <75 years 408
≥75 years to <85 years 401
≥85 years 124
[1]
Measure Analysis Population Description: Enrolled Set
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1415 participants
Female
436
  30.8%
Male
979
  69.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1415 participants
American Indian or Alaska Native
0
   0.0%
Asian
5
   0.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   0.1%
White
1282
  90.6%
More than one race
0
   0.0%
Unknown or Not Reported
126
   8.9%
1.Primary Outcome
Title Number of Clinically Stable Patients Whose Therapy Regimen Adheres to ESC Guideline Recommendations for Drug Types (Level 1) and Drug Type and Dose (Level 2) at Visit 1 (Before Referral to a Cardiologist)
Hide Description Assessment of treatment regimen with respect to ESC guideline adherence at Visit 1 before referral to cardiologist. ESC Criteria for adherence: Drug Types: Treatment with (1) ACEi or (1) ARB in combination with (1) beta-blocker and (1) MRA for patients w/an LVEF ≤ 35% at V1. Treatment w/(1) ACEi or (1) ARB, in combination with (1) beta-blocker+ without treatment with an MRA for patients with an LVEF > 35% at visit 1. Drug type & dose: Guideline adherent with respect to drug types and dosage of all respective guideline drugs ≥ 50% of the recommended target dose.
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled and Follow-up Set included. Due to missing left ventricular ejection fraction (LVEF) values, some patients could not be classified.
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Participants
Level 1: Drug Type : Adherent 110 59
Level 1: Drug type : Not Adherent 802 523
Patients missing LVEF values 503 279
2.Primary Outcome
Title Adherence to ESC Guideline at Visit 2 (After Referral to a Cardiologist, Month 6), for Follow-up Set: Drug Type and Drug Type and Dose
Hide Description Assessment of patients' adherence at Visit 2, for patients who were already adherent at Visit 1, and those who were not adherent at Visit 1, for both drug type and drug type and dose. ESC Criteria for adherence: Drug Types: Treatment with (1) ACEi or (1) ARB in combination with (1) beta-blocker and (1) MRA for patients w/an LVEF ≤ 35% at V1. Treatment w/(1) ACEi or (1) ARB, in combination with (1) beta-blocker+ without treatment with an MRA for patients with an LVEF > 35% at visit 1. Drug type & dose: Guideline adherent with respect to drug types and dosage of all respective guideline drugs ≥ 50% of the recommended target dose.
Time Frame Month 6
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Hide Analysis Population Description
Follow-Up set
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 861
Measure Type: Number
Unit of Measure: Percentage of Patients
Adherence at V2, not adherent at V1 for drug type 3.3
Adherence at V2, not adherent at V1:drug type/dose 0.8
Adherence at V2 and V1 for drug type 79.2
Adherence at Visit 1 for drug type & dose 86.7
3.Secondary Outcome
Title Duration of Heart Failure
Hide Description The duration of Heart Failure was collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Patients Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe. Patients who were considered clinically stable an with NT-proBNP levels > 600 pg/ml were referred to a cardiologist for evaluation and were in the follow-up set.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Participants
>3 years 896 549
≤3 years 517 312
4.Secondary Outcome
Title Number of Patients With Current Use of Concomitant Compound
Hide Description Use of concomitant compounds were collected at baseline (Visit 1)
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Participants
Diuretics - without mineral corticoid antagonists 934 625
Beta blocking agents 981 602
Agents acting on the renin-angiotensin system 834 491
Diuretics - mineral corticoid antagonists 664 416
Antithrombotic agents 401 256
Cardiac therapy 365 238
Lipid modifying agents 163 96
Mineral supplements 110 69
Calcium channel blockers 65 39
5.Secondary Outcome
Title Number of Follow-Up Patients With Current Use of Concomitant Compound at Visit 2
Hide Description Use of concomitant compounds were collected at 6 months (Visit 2)
Time Frame 6 months (Visit 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Follow-Up Set
Arm/Group Title Follow-Up Set Visit 2 (6 Months)
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml were referred to a cardiologist after 6 months (V2) for evaluation and were in the follow-up set
Overall Number of Participants Analyzed 753
Measure Type: Number
Unit of Measure: Participants
Diuretics - without mineral corticoid antagonists 581
Beta blocking agents 533
Agents acting on the renin-angiotensin system 476
Diuretics - mineral corticoid antagonists 423
Antithrombotic agents 221
Cardiac therapy 238
Lipid modifying agents 92
Mineral supplements 65
Calcium channel blockers 35
6.Secondary Outcome
Title Percentages of Clinically Stable Patients for Whom the Cardiologist and/or Primary Care Physician Optimizes Treatment Post Referral, Stratified According to Key Baseline Characteristics
Hide Description For patients who enter the prospective period of the study the post-referral treatment choice of cardiologists and/or primary care physicians was documented; for patients, for whom the cardiologist and/or primary care physician chose to prescribe a novel Heart Failure treatment, the treatment was assessed, if it fulfills the definition of adherence to European Society of Cardiology (ESC) guideline recommendation. The proportion of patients for whom an ESC guideline adherent treatment was de novo prescribed was assessed stratified according to different parameters.
Time Frame 6 months
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Hide Analysis Population Description
Follow-Up Set
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 861
Measure Type: Number
Unit of Measure: Percentage of Patients
Cardiologist's advice-No change 45.1
Cardiologist's advice-Treatment intensification 30.7
Cardiologist's advice-Treatment reduction 6.3
Cardiologist's advice-Treatment adaption 17.9
7.Secondary Outcome
Title Number of Patients With Different NT-proBNP Level Categories
Hide Description NT-proBNP levels (pg/ml) was measured at baseline in all consecutive patients who satisfy the inclusion and exclusion criteria. Measurements were performed on-site by means of a handheld device provided for the purposes of the study. NT-proBNP level categories could be 600 -799 pg/ml, 800 - 999 pg/ml, 1000 - 1200 pg/ml, > 1200 pg/ml).
Time Frame One measurement in all consecutive patients at baseline (Visit 1)
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Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Participants
<600 pg/ml 495 0
≥ 600 pg/ml to <800 pg/ml 135 130
≥ 800 pg/ml to <1000 pg/ml 97 93
≥ 1000 pg/ml to <1200 pg/ml 80 75
≥ 1200 pg/ml to <1400 pg/ml 48 46
≥ 1400 pg/ml to <1600 pg/ml 32 24
≥ 1600 pg/ml to <1800 pg/ml 33 33
≥ 1800 pg/ml to <2000 pg/ml 30 29
≥ 2000 pg/ml 465 431
8.Secondary Outcome
Title Percentages of Clinically Stable Patients
Hide Description Clinically stable patients in this study were defined as those patients for whom the primary care physician did not see a necessity (based on signs and symptoms of HF) to change the current pharmacological and/or device treatment of HF and who were on stable pharmacological and/or device treatment for HF for at least 3 months prior to inclusion.
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set
Arm/Group Title Enrolled Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Overall Number of Participants Analyzed 1415
Measure Type: Number
Unit of Measure: Percentage of Participants
Patients clinically stable 96.9
Patients not clinically stable 3.1
Patients suitable for prospective period of study 63.2
Patients not suitable for prospective period 36.8
9.Secondary Outcome
Title Number of Patients by Cardiologist Prescription Practice Per Country/Region
Hide Description The cardiologists' suggestions for pharmacological and/or device therapy for the treatment of clinically stable CHF patients was documented and assessed by means of descriptive statistical measures stratified by country/region 6 months after baseline.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Follow-Up Set
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 861
Measure Type: Number
Unit of Measure: Number of Participants
Western EU 198
Eastern EU 525
10.Secondary Outcome
Title Change of NT-proBNP Levels in Clinically Stable Chronic Heart Failure Patients With and Without Treatment Optimization 10 Months After Baseline
Hide Description At 10 months after baseline (end of study) NT-proBNP was assessed in clinically stable CHF patients with baseline NT-proBNP levels ≥ 600 pg/ml. Thus, for those patients two NT-proBNP measurements were available: at baseline and 10 months later. The individual change of NT-proBNP between both time points were assessed in accordance to the patients' treatment history during the study, i.e. baseline Heart Failure treatment and therapeutic decision taken 6 months after baseline.
Time Frame 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
Follow-Up Set
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 861
Mean (Standard Deviation)
Unit of Measure: pg/mL
NT-proBNP [pg/ml] at Visit 1 (Baseline) 2753  (2530)
NT-proBNP [pg/ml] at Visit 3 (10 months) 2245  (2303)
Absolute change in NT-proBNP (V3-V1) -504  (2607)
11.Secondary Outcome
Title Change in EuroQol Five Dimensions Questionnaire (EQ-5D) Total and Individual Sub-scores at Visit 1 (Baseline), Visit 2 (6 Months) and Visit 3 (10 Months)
Hide Description Quality of life (QoL) was assessed by EQ-5D including the dimensions mobility, self-care, usual activity, pain/discomfort, anxiety/depression. A utility index based on UK value sets was built to summarize the information of these five dimensions into a single scale. The utility index can range between -0.281 and 1.0 where a higher number indicates a better health status. In addition, a visual analog scale (VAS) was applied with a possible range between 0 (=worst imaginable health state) and 100 (=best imaginable health state). Scores collected for all patients at baseline (Visit 1) and at Visit 2 and Visit 3 (only patients who entered the prospective period of the study, i.e. clinically stable patients with a NT-proBNP level ≥ 600 pg/ml) were asked to fill out the EuroQol 5D (EQ-5D) quality of life (QoL) questionnaire validated for heart failure (HF).
Time Frame Baseline (Visit 1), 6 months (Visit 2), 10 months (Visit 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set for Visit 1 (Baseline) and Follow-Up Set (Visit 2 and 3) for those clinically stable patients who entered the prospective period of the study
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Median (Full Range)
Unit of Measure: Scores on a scale
EQ-5D Visual Analog Scale (VAS) - Visit 1 Number Analyzed 1411 participants 860 participants
60
(0 to 100)
60
(0.0 to 100)
EQ5D Utility index - Visit 1 Number Analyzed 1411 participants 860 participants
0.81
(-0.17 to 1.00)
0.79
(-0.17 to 1.00)
EQ5D Utility index - Visit 2 Number Analyzed 0 participants 747 participants
0.80
(-0.11 to 1.00)
EQ5D Utility index absolute change (V2-V1) Number Analyzed 0 participants 747 participants
0.00
(-0.47 to 0.83)
EQ5D Utility index - Visit 3 Number Analyzed 0 participants 569 participants
0.78
(0.28 to 1.00)
EQ5D Utility index absolute change (V3-V1) Number Analyzed 0 participants 567 participants
0.00
(-0.82 to 0.80)
12.Secondary Outcome
Title Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total and Individual Sub-scores at Visit 1 (Baseline), Visit 2 (6 Months) and Visit 3 (10 Months)
Hide Description The KCCQ is a self-administered questionnaire. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and quality of life, each with different Likert scale wording, including limitations, frequency, bother, change in condition, understanding, levels of enjoyment and satisfaction. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A positive change from baseline indicates improvement. Scores were collected for all patients at baseline and Visit 2 and Visit 3 (only patients who had entered the prospective period of the study (clinically stable patients with a NT-proBNP level ≥ 600 pg/ml) were asked to complete Kansas City Cardiomyopathy Questionnaire (KCCQ) validated for Heart Failure.
Time Frame Baseline (Visit 1), 6 months (Visit 2), 10 months (Visit 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set for Visit 1 (Baseline) and Follow-Up Set (Visit 2 and 3) for those clinically stable patients who entered the prospective period of the study
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Median (Full Range)
Unit of Measure: Utility Index Score
KCCQ Total Symptom Score - Visit 1 Number Analyzed 1413 participants 861 participants
77.1
(0 to 100)
74.0
(0 to 100)
KCCQ Clinical Summary Score - Visit 1 Number Analyzed 1413 participants 861 participants
72.1
(0 to 100)
68.8
(0 to 100)
KCCQ Overall Summary Score - Visit 1 Number Analyzed 1413 participants 861 participants
70.1
(4.2 to 100)
66.1
(4.2 to 100)
KCCQ Overall Summary Score absolute change (V2-V1) Number Analyzed 0 participants 747 participants
0.0
(-48.4 to 70.8)
KCCQ Overall Summary Score - Visit 3 Number Analyzed 0 participants 568 participants
66.7
(0.0 to 100)
KCCQ Overall Summary Score absolute change (V3-V1) Number Analyzed 0 participants 568 participants
0.5
(-66.1 to 66.8)
KCCQ Clinical Summary Score - Visit 2 Number Analyzed 0 participants 747 participants
68.8
(1.0 to 100.0)
KCCQ Clinical Summary Score abs. change (V2-V1) Number Analyzed 0 participants 747 participants
0.00
(-61.5 to 65.6)
KCCQ Clinical Summary Score - Visit 3 Number Analyzed 0 participants 568 participants
68.8
(0.0 to 100.0)
KCCQ Summary Score absolute change (V3-V1) Number Analyzed 0 participants 568 participants
0.0
(-53.1 to 69.0)
13.Secondary Outcome
Title Number of Patients in Different Living Conditions
Hide Description Living conditions were collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Living independently in household (alone) 313 204
Living with spouse or significant other 817 481
Living in residence with other family member 264 159
Living in a long term care facility 20 16
Transient housing 1 1
14.Secondary Outcome
Title Number of Patients in Different Employment Status
Hide Description Employment status was collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Student 0 0
Employed (part-time) 49 28
Employed (full-time) 144 51
Homemaker 26 15
Retired 1034 680
Unemployed 85 43
Sustained Sick Leave 73 40
Missing 4 4
15.Secondary Outcome
Title Number of Patients With Smoking Status
Hide Description Smoking status was collected at baseline (visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Never 779 500
Current 205 113
Former 427 246
Missing 4 2
16.Secondary Outcome
Title Number of Patients From Different Geographical Regions
Hide Description Geographic regions were collected at Baseline (Visit 1).
Time Frame Baseline (visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
RUS 226 173
BEL 201 114
HRV 169 95
SVN 122 72
POL 120 74
LTU 103 65
HUN 94 58
FRA 89 54
ESP 76 30
NOR 58 33
CYP 36 20
LVA 34 22
MLT 26 17
EST 18 16
DNK 19 4
PRT 13 6
17.Secondary Outcome
Title Number of Patients With Health Insurance Status
Hide Description Health insurance status was collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Statutory Health Insurance 1168 712
Private Health Insurance 29 22
Combined statutory and private health insurance 171 98
None 47 29
18.Secondary Outcome
Title Number of Patients at Different Educational Level
Hide Description Educational level was collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Primary Education 396 248
Secondary Education 730 421
University 257 173
None 30 17
Missing 2 2
19.Secondary Outcome
Title Number of Patients Per Primary Etiology of Heart Failure
Hide Description The primary etiology of Heart Failure was collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Primary Etiology- Ischemic 860 541
Primary Etiology-Non-Ischemic 553 320
20.Secondary Outcome
Title Number of Patients With Heart Failure (HF)-Related Hospitalizations in the Previous 12 Months Prior to Baseline, and During the Study
Hide Description HF-related hospitalizations was collected in the previous 12 months prior to baseline at baseline visit, at 6 and 10 months post-baseline.
Time Frame Baseline (Visit 1), 6 months, 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Number of Participants
Visit 1- Up to Baseline 383 262
Visit 2-6 months 0 18
Visit 3-10 months 0 22
Missing 0 6
21.Secondary Outcome
Title Percentage of Patients With Cardiovascular and Non-cardiovascular Co-morbidities
Hide Description Cardiovascular and non-cardiovascular co-morbidities were collected at baseline (Visit 1)
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 1415 861
Measure Type: Number
Unit of Measure: Percentage of Participants
Hypertension 74.2 75.8
Dyslipidemia 61.6 58.8
History of myocardial infarction 43.9 44.4
Atrial fibrillation 40.8 52.3
Obesity 36.1 30.8
Stable angina pectoris 31.4 33.8
Diabetes mellitus type 2 29.9 31.5
Other Comorbidities 13.0 14.0
22.Secondary Outcome
Title Mean Dose of Previously Taken and Current Use of Concomitant Medications
Hide Description Mean Dose of previously taken and current use of concomitant medications was to be collected at Visit 1, 6 months, 10 months post-baseline
Time Frame Baseline (Visit 1), 6 months, 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled Set and Follow-Up Set (Mean dose of concomitant medications was not collected/provided and could not be alternately computed based upon the information listed).
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description:
Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe.
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Number of Heart Failure (HF) Treatment Combinations
Hide Description The types and number of participants with HF treatment combinations were collected at Baseline (Visit 1).
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Follow-Up Set: Patients who were considered clinically stable and had NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Baseline (Visit 1) for evaluation.
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 861
Measure Type: Number
Unit of Measure: Number of Participants
One ACEi or one ARB and one beta-blocker(V1) 178
Exactly one beta-blocker and one MRA(V1) 166
Exactly one ACEi or one ARB and one MRA(V1) 165
One ACEi or (1)ARB & (1)MRA & (1)beta-blocker(V1) 82
Exactly one beta-blocker and ARNi(V1) 13
Exactly one MRA and ARNi(V1) 20
Exactly one MRA and one beta-blocker and ARNi(V1) 9
One ACEi or one ARB and one beta-blocker(V2) 156
Exactly one beta-blocker and one MRA(V2) 160
Exactly one ACEi or one ARB and one MRA(V2) 177
One ACEi or (1)ARB & (1)MRA & (1)beta-blocker(V2) 91
Exactly one beta-blocker and ARNi(V2) 17
Exactly one MRA and ARNi(V2) 23
Exactly one MRA and one beta-blocker and ARNi(V2) 10
One ACEi or one ARB and one beta-blocker(V3) 120
Exactly one beta-blocker and one MRA(V3) 130
Exactly one ACEi or one ARB and one MRA(V3) 143
One ACEi or (1)ARB & (1)MRA & (1)beta-blocker(V3) 77
Exactly one beta-blocker and ARNi(V3) 11
Exactly one MRA and ARNi(V3) 17
Exactly one MRA and one beta-blocker and ARNi(V3) 6
24.Secondary Outcome
Title Duration of Treatment With Device Type
Hide Description The duration of treatment with device type was collected at baseline (Visit 1)
Time Frame Baseline (Visit 1)
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Follow-Up Set (Data was not collected for this endpoint)
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
25.Secondary Outcome
Title Duration of Previously Taken and Currently Use of Most Common Non-Heart Failure Concomitant Compounds
Hide Description Duration of most common previously taken and current use of most common Non-HF concomitant compounds were collected
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Follow-Up Set
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 861
Measure Type: Number
Unit of Measure: Percentage of participants
Antithrombotic agents -≤1 and >3 years 0.65
Lipid modifying agents -≤1 and >3 years 0.57
Drugs for acid related disorders-≤1 and >3 years 0.31
26.Secondary Outcome
Title Number of Patients by Primary Care Physicians' Prescription Practice Per Country/Region
Hide Description For clinically stable CHF patients, the primary care physicians' prescription of pharmacological and device treatment for HF was to be documented prior to baseline and post cardiologist-referral. At the post-referral visit the degree of implementation of cardiologist-recommendations and the medical decision making (e.g. reasons for non-implementation) were to be documented.
Time Frame Baseline (Visit 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Follow-Up Set (Data was not collected for this endpoint.)
Arm/Group Title Follow-Up Set
Hide Arm/Group Description:
Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse Events were collected from FPFV to LPLV up to 2 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Enrolled Set Follow-Up Set
Hide Arm/Group Description Adult male and female patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who were managed in a primary care setting in sites across Europe. Patients who were considered clinically stable and with NT-proBNP levels > 600 pg/ml who were referred to a cardiologist at Visit 1 for evaluation were in the follow-up set.
All-Cause Mortality
Enrolled Set Follow-Up Set
Affected / at Risk (%) Affected / at Risk (%)
Total   32/1415 (2.26%)   30/861 (3.48%) 
Hide Serious Adverse Events
Enrolled Set Follow-Up Set
Affected / at Risk (%) Affected / at Risk (%)
Total   117/1415 (8.27%)   114/861 (13.24%) 
Blood and lymphatic system disorders     
Anaemia † 1  2/1415 (0.14%)  2/861 (0.23%) 
Cardiac disorders     
Acute myocardial infarction † 1  3/1415 (0.21%)  3/861 (0.35%) 
Angina pectoris † 1  1/1415 (0.07%)  1/861 (0.12%) 
Angina unstable † 1  1/1415 (0.07%)  1/861 (0.12%) 
Arrhythmia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Atrial fibrillation † 1  9/1415 (0.64%)  9/861 (1.05%) 
Atrioventricular block † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac arrest † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac failure † 1  29/1415 (2.05%)  27/861 (3.14%) 
Cardiac failure acute † 1  2/1415 (0.14%)  2/861 (0.23%) 
Cardiac failure chronic † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac failure congestive † 1  2/1415 (0.14%)  2/861 (0.23%) 
Myocardial infarction † 1  4/1415 (0.28%)  4/861 (0.46%) 
Palpitations † 1  1/1415 (0.07%)  1/861 (0.12%) 
Tachycardia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Ventricular extrasystoles † 1  1/1415 (0.07%)  1/861 (0.12%) 
Ventricular tachycardia † 1  2/1415 (0.14%)  2/861 (0.23%) 
Gastrointestinal disorders     
Constipation † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastric haemorrhage † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastric ulcer † 1  2/1415 (0.14%)  2/861 (0.23%) 
Melaena † 1  1/1415 (0.07%)  1/861 (0.12%) 
Short-bowel syndrome † 1  1/1415 (0.07%)  1/861 (0.12%) 
General disorders     
Chest discomfort † 1  1/1415 (0.07%)  1/861 (0.12%) 
Death † 1  3/1415 (0.21%)  2/861 (0.23%) 
Fatigue † 1  2/1415 (0.14%)  2/861 (0.23%) 
Oedema peripheral † 1  1/1415 (0.07%)  1/861 (0.12%) 
Soft tissue inflammation † 1  1/1415 (0.07%)  1/861 (0.12%) 
Sudden cardiac death † 1  1/1415 (0.07%)  1/861 (0.12%) 
Sudden death † 1  1/1415 (0.07%)  1/861 (0.12%) 
Ulcer haemorrhage † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hepatobiliary disorders     
Cholelithiasis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Infections and infestations     
Bacterial infection † 1  1/1415 (0.07%)  1/861 (0.12%) 
Epididymitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Erysipelas † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastroenteritis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Intestinal gangrene † 1  1/1415 (0.07%)  1/861 (0.12%) 
Orchitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Otitis externa † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pneumonia † 1  9/1415 (0.64%)  9/861 (1.05%) 
Respiratory tract infection † 1  1/1415 (0.07%)  1/861 (0.12%) 
Sepsis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Urinary tract infection † 1  1/1415 (0.07%)  1/861 (0.12%) 
Injury, poisoning and procedural complications     
Ankle fracture † 1  2/1415 (0.14%)  2/861 (0.23%) 
Electric shock † 1  1/1415 (0.07%)  1/861 (0.12%) 
Fall † 1  1/1415 (0.07%)  1/861 (0.12%) 
Fracture † 1  1/1415 (0.07%)  1/861 (0.12%) 
Head injury † 1  2/1415 (0.14%)  2/861 (0.23%) 
Humerus fracture † 1  1/1415 (0.07%)  1/861 (0.12%) 
Subarachnoid haemorrhage † 1  2/1415 (0.14%)  2/861 (0.23%) 
Wrist fracture † 1  1/1415 (0.07%)  1/861 (0.12%) 
Investigations     
International normalised ratio increased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Metabolism and nutrition disorders     
Diabetes mellitus † 1  3/1415 (0.21%)  3/861 (0.35%) 
Fluid overload † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hyponatraemia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Musculoskeletal and connective tissue disorders     
Arthritis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Back pain † 1  1/1415 (0.07%)  1/861 (0.12%) 
Lumbar spinal stenosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Brain neoplasm † 1  1/1415 (0.07%)  1/861 (0.12%) 
Breast cancer † 1  1/1415 (0.07%)  1/861 (0.12%) 
Neuroendocrine tumour † 1  1/1415 (0.07%)  1/861 (0.12%) 
Nervous system disorders     
Cerebrovascular accident † 1  4/1415 (0.28%)  4/861 (0.46%) 
Ischaemic stroke † 1  1/1415 (0.07%)  1/861 (0.12%) 
Syncope † 1  5/1415 (0.35%)  5/861 (0.58%) 
Product Issues     
Device malfunction † 1  1/1415 (0.07%)  1/861 (0.12%) 
Psychiatric disorders     
Delirium † 1  1/1415 (0.07%)  1/861 (0.12%) 
Renal and urinary disorders     
Acute kidney injury † 1  3/1415 (0.21%)  3/861 (0.35%) 
Renal failure † 1  1/1415 (0.07%)  1/861 (0.12%) 
Reproductive system and breast disorders     
Endometrial hyperplasia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Uterovaginal prolapse † 1  1/1415 (0.07%)  1/861 (0.12%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease † 1  4/1415 (0.28%)  3/861 (0.35%) 
Dyspnoea exertional † 1  1/1415 (0.07%)  1/861 (0.12%) 
Orthopnoea † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pulmonary mass † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pulmonary oedema † 1  3/1415 (0.21%)  3/861 (0.35%) 
Respiratory failure † 1  1/1415 (0.07%)  1/861 (0.12%) 
Skin and subcutaneous tissue disorders     
Ischaemic skin ulcer † 1  1/1415 (0.07%)  1/861 (0.12%) 
Social circumstances     
Homicide † 1  1/1415 (0.07%)  1/861 (0.12%) 
Surgical and medical procedures     
Aortic valve repair † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac ablation † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac pacemaker insertion † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac resynchronisation therapy † 1  2/1415 (0.14%)  2/861 (0.23%) 
Cardioversion † 1  1/1415 (0.07%)  1/861 (0.12%) 
Vascular disorders     
Circulatory collapse † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hypertension † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hypotension † 1  1/1415 (0.07%)  1/861 (0.12%) 
Peripheral artery thrombosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Vasculitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
1
Term from vocabulary, MedDRA (20.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Enrolled Set Follow-Up Set
Affected / at Risk (%) Affected / at Risk (%)
Total   187/1415 (13.22%)   181/861 (21.02%) 
Blood and lymphatic system disorders     
Anaemia † 1  6/1415 (0.42%)  6/861 (0.70%) 
Iron deficiency anaemia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cardiac disorders     
Arteriosclerosis coronary artery † 1  1/1415 (0.07%)  1/861 (0.12%) 
Atrial fibrillation † 1  5/1415 (0.35%)  5/861 (0.58%) 
Cardiac failure † 1  5/1415 (0.35%)  5/861 (0.58%) 
Cardio-respiratory arrest † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hypertensive cardiomyopathy † 1  1/1415 (0.07%)  1/861 (0.12%) 
Palpitations † 1  3/1415 (0.21%)  3/861 (0.35%) 
Tachyarrhythmia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Tachycardia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Ear and labyrinth disorders     
Tinnitus † 1  1/1415 (0.07%)  1/861 (0.12%) 
Vertigo † 1  6/1415 (0.42%)  6/861 (0.70%) 
Endocrine disorders     
Hypothyroidism † 1  1/1415 (0.07%)  1/861 (0.12%) 
Eye disorders     
Accommodation disorder † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cataract † 1  4/1415 (0.28%)  4/861 (0.46%) 
Diplopia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Sudden visual loss † 1  1/1415 (0.07%)  1/861 (0.12%) 
Visual acuity reduced † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastrointestinal disorders     
Abdominal discomfort † 1  1/1415 (0.07%)  1/861 (0.12%) 
Abdominal pain upper † 1  3/1415 (0.21%)  3/861 (0.35%) 
Abdominal wall haematoma † 1  1/1415 (0.07%)  1/861 (0.12%) 
Anal haemorrhage † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cheilitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Diarrhoea † 1  6/1415 (0.42%)  6/861 (0.70%) 
Dry mouth † 1  1/1415 (0.07%)  1/861 (0.12%) 
Dyspepsia † 1  2/1415 (0.14%)  2/861 (0.23%) 
Enterocolitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Functional gastrointestinal disorder † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastric ulcer † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastritis † 1  2/1415 (0.14%)  2/861 (0.23%) 
Gastroduodenitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastrointestinal angiodysplasia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Haematochezia † 1  2/1415 (0.14%)  2/861 (0.23%) 
Inguinal hernia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Melaena † 1  1/1415 (0.07%)  1/861 (0.12%) 
Nausea † 1  2/1415 (0.14%)  2/861 (0.23%) 
Oesophagitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Vomiting † 1  3/1415 (0.21%)  3/861 (0.35%) 
General disorders     
Adverse drug reaction † 1  1/1415 (0.07%)  1/861 (0.12%) 
Chest pain † 1  7/1415 (0.49%)  7/861 (0.81%) 
Fatigue † 1  9/1415 (0.64%)  9/861 (1.05%) 
Influenza like illness † 1  1/1415 (0.07%)  1/861 (0.12%) 
Localised oedema † 1  1/1415 (0.07%)  1/861 (0.12%) 
Oedema peripheral † 1  8/1415 (0.57%)  8/861 (0.93%) 
Pyrexia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Thirst † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hepatobiliary disorders     
Cholelithiasis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hepatic cirrhosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Infections and infestations     
Bronchitis † 1  10/1415 (0.71%)  10/861 (1.16%) 
Cellulitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cystitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Erysipelas † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gastroenteritis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gingivitis † 1  2/1415 (0.14%)  2/861 (0.23%) 
Influenza † 1  2/1415 (0.14%)  2/861 (0.23%) 
Lower respiratory tract infection † 1  2/1415 (0.14%)  2/861 (0.23%) 
Nasopharyngitis † 1  4/1415 (0.28%)  4/861 (0.46%) 
Onychomycosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Otitis media acute † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pharyngitis † 1  2/1415 (0.14%)  2/861 (0.23%) 
Pulpitis dental † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pyuria † 1  1/1415 (0.07%)  1/861 (0.12%) 
Respiratory tract infection † 1  2/1415 (0.14%)  2/861 (0.23%) 
Skin infection † 1  1/1415 (0.07%)  1/861 (0.12%) 
Tracheobronchitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Upper respiratory tract infection † 1  3/1415 (0.21%)  2/861 (0.23%) 
Urinary tract infection † 1  9/1415 (0.64%)  9/861 (1.05%) 
Viral infection † 1  1/1415 (0.07%)  1/861 (0.12%) 
Viral sinusitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Injury, poisoning and procedural complications     
Contusion † 1  1/1415 (0.07%)  1/861 (0.12%) 
Epicondylitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Ligament sprain † 1  1/1415 (0.07%)  1/861 (0.12%) 
Limb injury † 1  1/1415 (0.07%)  1/861 (0.12%) 
Rib fracture † 1  1/1415 (0.07%)  1/861 (0.12%) 
Investigations     
Blood creatine phosphokinase increased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Blood creatinine abnormal † 1  1/1415 (0.07%)  0/861 (0.00%) 
Blood creatinine increased † 1  3/1415 (0.21%)  3/861 (0.35%) 
Blood iron decreased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Blood pressure abnormal † 1  1/1415 (0.07%)  1/861 (0.12%) 
Blood pressure diastolic increased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Haemoglobin increased † 1  1/1415 (0.07%)  1/861 (0.12%) 
N-terminal prohormone brain natriuretic peptide increased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Prostatic specific antigen increased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Vitamin B12 decreased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Weight decreased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Weight increased † 1  2/1415 (0.14%)  2/861 (0.23%) 
Metabolism and nutrition disorders     
Diabetic metabolic decompensation † 1  1/1415 (0.07%)  1/861 (0.12%) 
Dyslipidaemia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gout † 1  2/1415 (0.14%)  2/861 (0.23%) 
Hyperkalaemia † 1  3/1415 (0.21%)  3/861 (0.35%) 
Hyperuricaemia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hypoglycaemia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hypokalaemia † 1  2/1415 (0.14%)  2/861 (0.23%) 
Obesity † 1  3/1415 (0.21%)  3/861 (0.35%) 
Type 2 diabetes mellitus † 1  2/1415 (0.14%)  2/861 (0.23%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  3/1415 (0.21%)  3/861 (0.35%) 
Back pain † 1  8/1415 (0.57%)  8/861 (0.93%) 
Cervical spinal stenosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Gouty arthritis † 1  3/1415 (0.21%)  3/861 (0.35%) 
Joint range of motion decreased † 1  1/1415 (0.07%)  1/861 (0.12%) 
Muscle spasms † 1  1/1415 (0.07%)  1/861 (0.12%) 
Muscular weakness † 1  1/1415 (0.07%)  1/861 (0.12%) 
Musculoskeletal pain † 1  1/1415 (0.07%)  0/861 (0.00%) 
Neck pain † 1  1/1415 (0.07%)  1/861 (0.12%) 
Osteitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Osteoarthritis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Osteoporosis † 1  2/1415 (0.14%)  2/861 (0.23%) 
Rotator cuff syndrome † 1  1/1415 (0.07%)  1/861 (0.12%) 
Spinal pain † 1  1/1415 (0.07%)  1/861 (0.12%) 
Temporomandibular joint syndrome † 1  1/1415 (0.07%)  1/861 (0.12%) 
Tendon disorder † 1  1/1415 (0.07%)  1/861 (0.12%) 
Tendonitis † 1  2/1415 (0.14%)  2/861 (0.23%) 
Torticollis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer † 1  1/1415 (0.07%)  1/861 (0.12%) 
Squamous cell carcinoma † 1  1/1415 (0.07%)  1/861 (0.12%) 
Nervous system disorders     
Carotid artery stenosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cervical radiculopathy † 1  1/1415 (0.07%)  1/861 (0.12%) 
Dizziness † 1  5/1415 (0.35%)  5/861 (0.58%) 
Headache † 1  15/1415 (1.06%)  15/861 (1.74%) 
Hypoaesthesia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Leukoencephalopathy † 1  1/1415 (0.07%)  1/861 (0.12%) 
Syncope † 1  1/1415 (0.07%)  1/861 (0.12%) 
Psychiatric disorders     
Anxiety † 1  12/1415 (0.85%)  12/861 (1.39%) 
Anxiety disorder † 1  2/1415 (0.14%)  2/861 (0.23%) 
Bipolar disorder † 1  1/1415 (0.07%)  1/861 (0.12%) 
Confusional state † 1  1/1415 (0.07%)  1/861 (0.12%) 
Depression † 1  2/1415 (0.14%)  2/861 (0.23%) 
Hallucination, visual † 1  1/1415 (0.07%)  1/861 (0.12%) 
Insomnia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Nightmare † 1  1/1415 (0.07%)  1/861 (0.12%) 
Renal and urinary disorders     
Acute kidney injury † 1  1/1415 (0.07%)  1/861 (0.12%) 
Chronic kidney disease † 1  2/1415 (0.14%)  2/861 (0.23%) 
Nephropathy † 1  2/1415 (0.14%)  2/861 (0.23%) 
Nocturia † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pollakiuria † 1  2/1415 (0.14%)  2/861 (0.23%) 
Renal colic † 1  1/1415 (0.07%)  1/861 (0.12%) 
Renal failure † 1  4/1415 (0.28%)  4/861 (0.46%) 
Urinary retention † 1  1/1415 (0.07%)  1/861 (0.12%) 
Respiratory, thoracic and mediastinal disorders     
Asthma † 1  1/1415 (0.07%)  1/861 (0.12%) 
Bronchiectasis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Catarrh † 1  2/1415 (0.14%)  2/861 (0.23%) 
Chronic obstructive pulmonary disease † 1  5/1415 (0.35%)  5/861 (0.58%) 
Chronic respiratory failure † 1  1/1415 (0.07%)  1/861 (0.12%) 
Cough † 1  6/1415 (0.42%)  6/861 (0.70%) 
Dyspnoea † 1  2/1415 (0.14%)  2/861 (0.23%) 
Dyspnoea at rest † 1  2/1415 (0.14%)  2/861 (0.23%) 
Dyspnoea exertional † 1  9/1415 (0.64%)  9/861 (1.05%) 
Dyspnoea paroxysmal nocturnal † 1  2/1415 (0.14%)  2/861 (0.23%) 
Epistaxis † 1  3/1415 (0.21%)  3/861 (0.35%) 
Haemoptysis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Nasal congestion † 1  1/1415 (0.07%)  1/861 (0.12%) 
Nocturnal dyspnoea † 1  1/1415 (0.07%)  1/861 (0.12%) 
Oropharyngeal pain † 1  2/1415 (0.14%)  2/861 (0.23%) 
Orthopnoea † 1  3/1415 (0.21%)  3/861 (0.35%) 
Pleural effusion † 1  1/1415 (0.07%)  1/861 (0.12%) 
Productive cough † 1  2/1415 (0.14%)  2/861 (0.23%) 
Rales † 1  2/1415 (0.14%)  2/861 (0.23%) 
Rhinitis allergic † 1  1/1415 (0.07%)  1/861 (0.12%) 
Rhinorrhoea † 1  2/1415 (0.14%)  2/861 (0.23%) 
Skin and subcutaneous tissue disorders     
Blister † 1  1/1415 (0.07%)  1/861 (0.12%) 
Decubitus ulcer † 1  1/1415 (0.07%)  1/861 (0.12%) 
Dermatitis † 1  2/1415 (0.14%)  2/861 (0.23%) 
Dermatitis contact † 1  1/1415 (0.07%)  1/861 (0.12%) 
Ingrowing nail † 1  1/1415 (0.07%)  1/861 (0.12%) 
Pruritus † 1  3/1415 (0.21%)  3/861 (0.35%) 
Skin ulcer † 1  2/1415 (0.14%)  2/861 (0.23%) 
Urticaria † 1  1/1415 (0.07%)  1/861 (0.12%) 
Surgical and medical procedures     
Cataract operation † 1  2/1415 (0.14%)  2/861 (0.23%) 
Coronary angioplasty † 1  1/1415 (0.07%)  1/861 (0.12%) 
Dental operation † 1  1/1415 (0.07%)  1/861 (0.12%) 
Intraocular lens implant † 1  1/1415 (0.07%)  1/861 (0.12%) 
Vascular disorders     
Aortic aneurysm † 1  1/1415 (0.07%)  1/861 (0.12%) 
Deep vein thrombosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Hypertension † 1  6/1415 (0.42%)  3/861 (0.35%) 
Hypotension † 1  6/1415 (0.42%)  6/861 (0.70%) 
Peripheral arterial occlusive disease † 1  1/1415 (0.07%)  1/861 (0.12%) 
Peripheral vascular disorder † 1  1/1415 (0.07%)  1/861 (0.12%) 
Thrombophlebitis † 1  1/1415 (0.07%)  1/861 (0.12%) 
Varicose vein † 1  1/1415 (0.07%)  1/861 (0.12%) 
Venous thrombosis † 1  1/1415 (0.07%)  1/861 (0.12%) 
1
Term from vocabulary, MedDRA (20.1)
†
Indicates events were collected by systematic assessment
The recruitment was to be regarded as completed once approx. 2400 patients had entered the prospective period. However it was decided by Novartis to terminate the study prematurely, in March 2018.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02807857    
Other Study ID Numbers: CLCZ696B3402
2016-000473-20 ( EudraCT Number )
First Submitted: June 17, 2016
First Posted: June 21, 2016
Results First Submitted: March 21, 2019
Results First Posted: January 5, 2021
Last Update Posted: February 24, 2021