Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 )

Tracking Information
First Submitted Date  ICMJE June 17, 2016
First Posted Date  ICMJE June 21, 2016
Results First Submitted Date  ICMJE March 21, 2019
Results First Posted Date  ICMJE January 5, 2021
Last Update Posted Date February 24, 2021
Actual Study Start Date  ICMJE July 7, 2016
Actual Primary Completion Date March 23, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
  • 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) [ Time Frame: Baseline (Visit 1) ]
    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.
  • 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 [ Time Frame: Month 6 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
Change of the percentage of clinically stable patients whose therapy regimen adheres to ESC guideline recommendations before and after specialist referral [ Time Frame: Baseline, Month 6 ]
Assessment of patients' treatment regimen with respect to ESC guideline adherence at baseline (Visit 1) and after referral to a specialist (visit 2); the change between both visits will be calculated to reflect the proportion of patients for whom optimization was deemed necessary and implemented.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
  • Duration of Heart Failure [ Time Frame: Baseline (Visit 1) ]
    The duration of Heart Failure was collected at Baseline (Visit 1).
  • Number of Patients With Current Use of Concomitant Compound [ Time Frame: Baseline (Visit 1) ]
    Use of concomitant compounds were collected at baseline (Visit 1)
  • Number of Follow-Up Patients With Current Use of Concomitant Compound at Visit 2 [ Time Frame: 6 months (Visit 2) ]
    Use of concomitant compounds were collected at 6 months (Visit 2)
  • Percentages of Clinically Stable Patients for Whom the Cardiologist and/or Primary Care Physician Optimizes Treatment Post Referral, Stratified According to Key Baseline Characteristics [ Time Frame: 6 months ]
    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.
  • Number of Patients With Different NT-proBNP Level Categories [ Time Frame: One measurement in all consecutive patients at baseline (Visit 1) ]
    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).
  • Percentages of Clinically Stable Patients [ Time Frame: Baseline (Visit 1) ]
    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.
  • Number of Patients by Cardiologist Prescription Practice Per Country/Region [ Time Frame: 6 months ]
    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.
  • Change of NT-proBNP Levels in Clinically Stable Chronic Heart Failure Patients With and Without Treatment Optimization 10 Months After Baseline [ Time Frame: 10 months ]
    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.
  • 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) [ Time Frame: Baseline (Visit 1), 6 months (Visit 2), 10 months (Visit 3) ]
    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).
  • 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) [ Time Frame: Baseline (Visit 1), 6 months (Visit 2), 10 months (Visit 3) ]
    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.
  • Number of Patients in Different Living Conditions [ Time Frame: Baseline (Visit 1) ]
    Living conditions were collected at Baseline (Visit 1).
  • Number of Patients in Different Employment Status [ Time Frame: Baseline (Visit 1) ]
    Employment status was collected at Baseline (Visit 1).
  • Number of Patients With Smoking Status [ Time Frame: Baseline (Visit 1) ]
    Smoking status was collected at baseline (visit 1).
  • Number of Patients From Different Geographical Regions [ Time Frame: Baseline (visit 1) ]
    Geographic regions were collected at Baseline (Visit 1).
  • Number of Patients With Health Insurance Status [ Time Frame: Baseline (Visit 1) ]
    Health insurance status was collected at Baseline (Visit 1).
  • Number of Patients at Different Educational Level [ Time Frame: Baseline (Visit 1) ]
    Educational level was collected at Baseline (Visit 1).
  • Number of Patients Per Primary Etiology of Heart Failure [ Time Frame: Baseline (Visit 1) ]
    The primary etiology of Heart Failure was collected at Baseline (Visit 1).
  • Number of Patients With Heart Failure (HF)-Related Hospitalizations in the Previous 12 Months Prior to Baseline, and During the Study [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    HF-related hospitalizations was collected in the previous 12 months prior to baseline at baseline visit, at 6 and 10 months post-baseline.
  • Percentage of Patients With Cardiovascular and Non-cardiovascular Co-morbidities [ Time Frame: Baseline (Visit 1) ]
    Cardiovascular and non-cardiovascular co-morbidities were collected at baseline (Visit 1)
  • Mean Dose of Previously Taken and Current Use of Concomitant Medications [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    Mean Dose of previously taken and current use of concomitant medications was to be collected at Visit 1, 6 months, 10 months post-baseline
  • Number of Heart Failure (HF) Treatment Combinations [ Time Frame: Baseline (Visit 1) ]
    The types and number of participants with HF treatment combinations were collected at Baseline (Visit 1).
  • Duration of Treatment With Device Type [ Time Frame: Baseline (Visit 1) ]
    The duration of treatment with device type was collected at baseline (Visit 1)
  • Duration of Previously Taken and Currently Use of Most Common Non-Heart Failure Concomitant Compounds [ Time Frame: Baseline (Visit 1) ]
    Duration of most common previously taken and current use of most common Non-HF concomitant compounds were collected
  • Number of Patients by Primary Care Physicians' Prescription Practice Per Country/Region [ Time Frame: Baseline (Visit 1) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
  • Number of patients in different age categories [ Time Frame: Baseline ]
    Age in years will be collected at Baseline (Visit 1) in patients who enter the prospective period, i.e. clinically stable patients with NT-proBNP > or = 600 pg/mL
  • Duration of Heart Failure [ Time Frame: Baseline (Visit 1) ]
    The duration of Heart Failure is collected at Baseline (Visit 1).
  • Number of patients with previously taken and current use of concomitant compound [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    Previously taken and current use of concomitant compound will be collected at baseline (Visit), 6 and 10 months post-baseline.
  • Percentages of clinically stable patients for whom the cardiologist and/or primary care physician optimizes treatment post referral, stratified according to key baseline characteristics [ Time Frame: 6 and 10 months ]
    For patients who enter the prospective period of the study the post-referral treatment choice of cardiologists and/or primary care physicians will be documented; for patients, for whom the cardiologist and/or primary care physician chose to prescribe a novel Heart Failure treatment, the treatment will be 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 will be assessed stratified according to different parameters.
  • Number of patients with different NT-proBNP level categories [ Time Frame: One measurement in all consecutive patients at baseline (Visit 1) ]
    NT-proBNP levels (pg/ml) will be measured at baseline in all consecutive patients who satisfy the inclusion and exclusion criteria. Measurements are 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).
  • Percentages of clinically stable patients [ Time Frame: Baseline (Visit 1) ]
    Clinically stable patients in this study are defined as those patients for whom the primary care physician does not see a necessity (based on signs and symptoms of HF) to change the current pharmacological and/or device treatment of HF and who have been on stable pharmacological and/or device treatment for HF for at least 3 months prior to inclusion.
  • Number of patients by cardiologist prescription practice per country/region [ Time Frame: 6 months ]
    The cardiologists' suggestions for pharmacological and/or device therapy for the treatment of clinically stable CHF patients will be documented and assessed by means of descriptive statistical measures stratified by country/region 6 months after baseline.
  • Number of patients by primary care physicians' prescription practice per country/region [ Time Frame: Baseline, 6 months, 10 months ]
    For clinically stable CHF patients, the primary care physicians' prescription of pharmacological and device treatment for HF will be documented prior to (at baseline) and post cardiologist-referral (6 and 10 months after baseline). At the post-referral visit the degree of implementation of cardiologist-recommendations and the medical decision making (e.g. reasons for non-implementation) will be documented.
  • Change of NT-proBNP levels in clinically stable CHF patients with and without treatment optimization 10 months after baseline [ Time Frame: Baseline (Visit 1) and 10 months ]
    At 10 months after baseline (end of study) NT-proBNP will again be assessed in clinically stable CHF patients with baseline NT-proBNP levels ≥ 600 pg/ml. Thus, for those patients two NT-proBNP measurements will be available: at baseline and 10 months later. The individual change of NT-proBNP between both time points will be 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.
  • Change of EQ-5D total and individual sub-scores between baseline and 6 months later, between baseline and 10 months later [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    At baseline (all patients) and at Visit 2 and Visit 3 (only patients who have entered the prospective period of the study, i.e. clinically stable patients with a NT-proBNP level ≥ 600 pg/ml) will be asked to fill out the EuroQol 5D (EQ-5D) and Kansas City Cardiomyopathy Questionnaire (KCCQ) - two quality of life (QoL) questionnaires validated for HF.
  • Change in KCCQ total and individual sub-scores between baseline and 6 months later, between and 10 months later [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    At baseline (all patients) and at Visit 2 and Visit 3 (only patients who have entered the prospective period of the study, i.e. clinically stable patients with a NT-proBNP level ≥ 600 pg/ml) will be asked to fill out the EuroQol 5D (EQ-5D) and Kansas City Cardiomyopathy Questionnaire (KCCQ) - two quality of life (QoL) questionnaires validated for Heart Failure.
  • Number of patients with different gender categories [ Time Frame: Baseline (Visit 1) ]
    Gender will be collected at Baseline (Visit 1).
  • Number of patients with different ethnicity [ Time Frame: Baseline (Visit 1) ]
    Race/Ethnicity will be collected at Baseline (Visit 1).
  • Number of patients in different living conditions [ Time Frame: Baseline (Visit 1) ]
    Living conditions will be collected at Baseline (Visit 1).
  • Number of patients in different employment status [ Time Frame: Baseline (Visit 1) ]
    Employment status will be collected at Baseline (Visit 1).
  • Number of patients with smoking status [ Time Frame: Baseline (Visit 1) ]
    Smoking status will be collected at baseline (visit 1).
  • Number of patients from different geographical regions [ Time Frame: Baseline (visit 1) ]
    Geographic regions will be collected at Baseline (Visit 1).
  • Number of patients with health insurance status [ Time Frame: Baseline (Visit 1) ]
    Health insurance status will be collected at Baseline (Visit 1).
  • Number of patients at different educational level [ Time Frame: Baseline (Visit 1) ]
    Educational level will be collected at Baseline (Visit 1).
  • Number of patients per primary etiology of Heart Failure [ Time Frame: Baseline (Visit 1) ]
    The primary etiology of Heart Failure will be collected at Baseline (Visit 1).
  • Number of heart failure (HF)-related hospitalizations in the previous 12 months prior to baseline, and during the study [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    HF-related hospitalizations will collected in the previous 12 months prior to baseline at baseline visit, at 6 and 10 months post-baseline.
  • Number of patients with cardiovascular and non-cardiovascular co-morbidities [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    Cardiovascular and non-cardiovascular co-morbidities will be collected at baseline (Visit 1), 6 and 10 months post-baseline.
  • Mean dose of previously taken and current use of concomitant compound [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    The mean dose of previously taken and current use of concomitant compound, will be collected at Baseline (Visit 1), 6 and 10 months post-baseline.
  • Number of device type [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    The numbers of device type will be collected at Baseline (Visit 1), at 6 and 10 months post-baseline.
  • Duration of treatment with device type [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    The duration of treatment with device type will be collected at baseline (Visit 1), at 6 and 10 months post-baseline.
  • Duration of previously taken and currently use of concomitant compound [ Time Frame: Baseline (Visit 1), 6 months, 10 months ]
    Duration of previously taken and current use of concomitant compound, will be collected at Baseline (Visit 1), 6 and 10 months post-baseline.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Prospective Evaluation of Natriuretic Peptide Based Referral of CHF Patients in Primary Care
Official Title  ICMJE A Prospective Evaluation of Natriuretic Peptide Based Referral of CHF Patients in Primary Care
Brief Summary This low interventional study, whose unique intervention was to measure the blood level of a biomarker called NT-proBNP in chronic heart failure patients daily followed-up by Primary Care Physicians (PCPs) in Europe, assessed if the cardiologist referral guided by NT-proBNP measurement in patients who were currently judged by PCPs as being stable, would lead to optimization of HF treatment, defined in adherence to treatment recommendations of the current European Society of Cardiology guidelines for the treatment of heart failure.
Detailed Description In the majority of European countries, the primary management of chronic heart failure patients was performed by General Practitioners in collaboration with cardiologists (specialists). Previous studies had shown that many patients suffering from CHF do not receive optimal pharmacological and/or device treatment for their disease. An increase in natriuretic peptides (BNP, NT-proBNP) was associated with increased risk of cardiovascular events in heart failure patients. The purpose of the present study was to assess if a referral of clinical stable chronic heart failure patients with reduced ventricular ejection fraction (EF < or = 40%) and NT-proBNP level > or = 600 pg/mL to a specialist (cardiologist) led to treatment optimization, defined as adherence to the treatment recommendations according to the European Society of Cardiology (ESC) guidelines. In addition, data obtained in this study was used to describe demographic, clinical (including NT-proBNP levels) and treatment characteristics of CHF patients who were managed in the primary care setting across Europe..
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Chronic Heart Failure (CHF)
Intervention  ICMJE Procedure: Standard care
Patients will receive the treatment that their primary care physician has decided to prescribe for their disease
Study Arms  ICMJE Patients' heart failure and non-heart failure
No treatments are stipulated by this protocol - patients' HF and non-HF treatments will be observed throughout the study. The patients' treatment is entirely in the discretion of the primary care physicians
Intervention: Procedure: Standard care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 8, 2020)
1415
Original Estimated Enrollment  ICMJE
 (submitted: June 17, 2016)
4000
Actual Study Completion Date  ICMJE March 23, 2018
Actual Primary Completion Date March 23, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to provide written informed consent and accept study procedures and time schedule.
  • Age ≥ 18 years.
  • Patients suffering from chronic heart failure (the heart failure diagnosis must have been made or confirmed by a cardiologist and/or hospital physician at any time in the patient's medical history).
  • Patients with reduced ejection fraction (≤ 40%) as confirmed at any time point in the patient's medical history.

Exclusion Criteria:

  • Use of investigational drugs either within 5 half-lives of enrollment, or within 30 days, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
  • Major surgery in the last 3 months prior to baseline or planned major surgery or cardiac intervention during the study.
  • Cancer or other significant co-morbidities implying that the patient's condition is unstable.
  • Comorbidities that can be associated with elevated natriuretic peptide (NP) levels: renal insufficiency, (eGFR < 25 ml/min/1.73 m² calculated according to MDRD formula), recent (less than 3 months) cerebral trauma or recent (less than 3 months) cerebrovascular incident, novel diagnosis or acute exacerbation of COPD within the last 3 months.
  • Patients who are primarily managed and regularly followed-up by a cardiologist for their HF
  • Highly frail patients whose estimated lifespan due to comorbidities by the judgement of the investigator is less than 6 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Croatia,   Cyprus,   Denmark,   Estonia,   France,   Hungary,   Israel,   Italy,   Latvia,   Lithuania,   Malta,   Norway,   Poland,   Portugal,   Russian Federation,   Slovenia,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02807857
Other Study ID Numbers  ICMJE CLCZ696B3402
2016-000473-20 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP