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Candesartan Cilexetil Special Drug Use Surveillance 「Challenge - Quality Control」

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ClinicalTrials.gov Identifier: NCT02211638
Recruitment Status : Completed
First Posted : August 7, 2014
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Hypertension
Intervention Drug: Candesartan Cilexetil
Enrollment 18113
Recruitment Details Participants took part in the study at 1503 investigative sites in Japan, from 13-Jun-2011 to 25-Apr-2013.
Pre-assignment Details Participants with a diagnosis of hypertension were enrolled to receive candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily for up to the last dose of study drug (up to Month 6).
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Period Title: Overall Study
Started 18113
Completed 17130
Not Completed 983
Reason Not Completed
Case Report Forms Uncollected             291
Protocol Violation             692
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Baseline Participants 17130
Hide Baseline Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17130 participants
65.9  (12.85)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Female
8640
  50.4%
Male
8490
  49.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 17130 participants
17130
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 17130 participants
61.3  (13.46)
Smoking Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Never Smoked
11683
  68.2%
Current Smoker
2032
  11.9%
Unknown
3415
  19.9%
Medical Complications   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Had no Medical Complications
7988
  46.6%
Had Medical Complications
9142
  53.4%
[1]
Measure Description: Complications defined as a disease or a health condition for each participant at the start of study. Complications were classified as congenital anomalies, endocrine disorders, hematologic disorders, psychiatric and nervous system disorders, cardiovascular disorders, respiratory disorders, gastrointestinal (GI) disorders, renal disease and other complications. Other complications included all complications except for those mentioned above. Participants may be represented in more than 1 category.
Medical History   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Had no Medical History
14376
  83.9%
Had Medical History
2754
  16.1%
[1]
Measure Description: Medical history defined as a disease or a health condition for each participant before start of the study. Medical history was classified as congenital anomalies, hematologic disorders, psychiatric and nervous system disorders, cardiovascular disorders, respiratory disorders, GI disorders, hepatic and biliary disorders, renal disease and other medical history. Other medical history included all medical history except for those mentioned above. Participants may be represented in more than 1 category.
Initial Dose of Study Drug  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
2mg/day
528
   3.1%
4mg/day
4865
  28.4%
8mg/day
11170
  65.2%
12mg/day
556
   3.2%
Other Initial Dose
11
   0.1%
Concomitant Antihypertensive Drugs  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Had no Concomitant Antihypertensive Drugs
11968
  69.9%
Had Concomitant Antihypertensive Drugs
5162
  30.1%
Switching Antihypertensive Drugs  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Had no Switching Antihypertensive Drugs
12856
  75.0%
Had Switching Antihypertensive Drugs
4274
  25.0%
Status of Administration of Antihypertensive Drugs   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Had no Antihypertensive Drugs
10055
  58.7%
Had Antihypertensive Drugs
7075
  41.3%
[1]
Measure Description: Had no Antihypertensive Drugs; Participants who had not received concomitant antihypertensive drugs and switching antihypertensive drugs prior to the start of study drug were reported. Had Antihypertensive Drugs; Participants who had received concomitant antihypertensive drugs or switching antihypertensive drugs prior to the start of study drug were reported.
Clinical Systolic Blood Pressure (SBP) (Sitting)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 17130 participants
156.1  (18.67)
Clinical Diastolic Blood Pressure (DBP) (Sitting)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 17130 participants
88.7  (13.47)
Early Morning Home SBP (Ave)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 17130 participants
153.9  (15.89)
Early Morning Home DBP (Ave)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 17130 participants
89.4  (11.41)
Evening Home SBP (Ave)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 17130 participants
146.2  (15.88)
Evening Home DBP (Ave)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 17130 participants
85.5  (11.59)
Spot Urine Sodium: NaS  
Mean (Standard Deviation)
Unit of measure:  mEq/L
Number Analyzed 17130 participants
129.9  (52.78)
Spot Urine Creatinine: CrS  
Mean (Standard Deviation)
Unit of measure:  mg/L
Number Analyzed 17130 participants
804.2  (1002.82)
Estimated 24hr Creatinine Excretion: UCr24   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/day
Number Analyzed 17130 participants
1099.52  (349.732)
[1]
Measure Description: UCr24 = -2.04×age(years)+14.89×weight(kg)+16.14×height(cm)-2244.45
Estimated 24hr Sodium Excretion: UNa24   [1] 
Mean (Standard Deviation)
Unit of measure:  mEq/day
Number Analyzed 17130 participants
230.70  (246.267)
[1]
Measure Description: UNa24 = 21.98×[(NaS/CrS) ×UCr24]^0.392
Salt Intake: NaCl24   [1] 
Mean (Standard Deviation)
Unit of measure:  G/day
Number Analyzed 17130 participants
13.5  (14.41)
[1]
Measure Description: NaCl24 = UNa24×0.0585
Salt Intake: NaCl24   [1] 
Mean (Standard Deviation)
Unit of measure:  G/day
Number Analyzed 17130 participants
10.0  (2.92)
[1]
Measure Description: NaCl24 = UNa24×0.0585 10 <= Spot Urine Sodium (mEq/L) < 500, 100 <= Spot Urine Creatinine (mg/L) < 5000
Focus on Blood Pressure (BP) Measurement   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17130 participants
Focus on Home BP than Clinic BP
7614
  44.4%
Focus on Clinic BP than Home BP
8021
  46.8%
Other
1495
   8.7%
[1]
Measure Description: Participants who were answered Home or Clinic for a question" Which blood pressure are you focusing on?" were reported.
1.Primary Outcome
Title Changes in Clinic Blood Pressure in the Sitting Position
Hide Description Changes in clinic blood pressure (systolic blood pressure –SBP and diastolic blood pressure -DBP) in the sitting position measured at Month 3, last dose of candesartan (up to Month 6) relative to baseline were reported.
Time Frame Baseline, Month 3 and Last dose of Candesartan (up to Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study. Analysis population was all participants in safety analysis set who were assessed with this outcome measure. Here 'n' is number of participants analyzed at the given timepoint.
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description:
Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Participants Analyzed 16617
Mean (Standard Deviation)
Unit of Measure: mmHg
Month 3, SBP Number Analyzed 14055 participants
-20.1  (19.30)
Last Dose of Candesartan, SBP Number Analyzed 15211 participants
-18.1  (18.91)
Month 3, DBP Number Analyzed 14055 participants
-10.4  (12.34)
Last Dose of Candesartan, DBP Number Analyzed 15211 participants
-9.3  (12.12)
2.Primary Outcome
Title Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Continued Candesartan Therapy at Week 14
Hide Description Changes in clinic blood pressure (systolic blood pressure –SBP and diastolic blood pressure -DBP) in the sitting position measured at Month 3, last dose of candesartan (up to Month 6) relative to baseline in only participants who continued candesartan therapy at Week 14 were reported.
Time Frame Baseline, Month 3 and Last dose of Candesartan (up to Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study. Analysis population was participants in safety analysis set who continued candesartan therapy at Week 14 and were assessed with this outcome measure. Here 'n' is number of participants analyzed at the given timepoint.
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description:
Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Participants Analyzed 11753
Mean (Standard Deviation)
Unit of Measure: mmHg
Month 3, SBP Number Analyzed 10677 participants
-19.8  (18.74)
Last Dose of Candesartan, SBP Number Analyzed 11677 participants
-19.5  (18.64)
Month 3, DBP Number Analyzed 10677 participants
-10.1  (12.01)
Last Dose of Candesartan, DBP Number Analyzed 11677 participants
-10.0  (12.03)
3.Primary Outcome
Title Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Switched to ARB Combination Drug Therapy at Week 14
Hide Description Changes in clinic blood pressure (systolic blood pressure –SBP and diastolic blood pressure -DBP) in the sitting position measured at Month 3, last dose of candesartan and last dose of ARB Combination Drug (up to Month 6) relative to baseline were reported. The data was for only participants who switched to ARB combination drug therapy from candesartan therapy at Week 14 as part of routine medical care.
Time Frame Baseline, Month 3, Last dose of Candesartan, and Last dose of ARB Combination Drug (up to Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study. Analysis population was participants in safety analysis set who switched to ARB combination drug therapy from candesartan therapy at Week 14 and were assessed with this outcome measure. Here 'n' is number of participants analyzed at the given timepoint.
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description:
Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Participants Analyzed 3630
Mean (Standard Deviation)
Unit of Measure: mmHg
Month 3, SBP Number Analyzed 3060 participants
-21.7  (20.74)
Last Dose of Candesartan, SBP Number Analyzed 2496 participants
-12.3  (18.83)
Last dose of ARB Combination Drug, SBP Number Analyzed 3464 participants
-26.4  (20.49)
Month 3, DBP Number Analyzed 3060 participants
-11.8  (13.26)
Last Dose of Candesartan, DBP Number Analyzed 2496 participants
-6.4  (12.04)
Last dose of ARB Combination Drug, DBP Number Analyzed 3464 participants
-14.4  (13.45)
4.Primary Outcome
Title Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Switched to Diuretic-containing ARB Combination Drug Therapy at Week 14
Hide Description Changes in clinic blood pressure (systolic blood pressure –SBP and diastolic blood pressure -DBP) in the sitting position measured at last dose of diuretic-containing ARB combination drug (up to Month 6) relative to baseline were reported. The data was for only participants who switched to diuretic-containing ARB combination drug therapy from candesartan therapy at Week 14 as part of routine medical care.
Time Frame Baseline and Last dose of ARB Combination Drug (up to Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study. Analysis population was participants in safety analysis set who switched to diuretic-containing ARB combination drug therapy from candesartan therapy at Week 14 and were assessed with this outcome measure.
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description:
Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Participants Analyzed 984
Mean (Standard Deviation)
Unit of Measure: mmHg
SBP -24.5  (20.20)
DBP -13.2  (13.62)
5.Primary Outcome
Title Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Switched to Calcium Channel Blocker (CCB)-Containing ARB Combination Drug Therapy at Week 14
Hide Description Changes in clinic blood pressure (systolic blood pressure –SBP and diastolic blood pressure -DBP) in the sitting position measured at last dose of ARB combination drug (up to Month 6) relative to baseline were reported. The data was for only participants who switched to calcium channel blocker (CCB)-containing ARB combination drug therapy from candesartan therapy at Week 14 as part of routine medical care.
Time Frame Baseline and Last dose of ARB Combination Drug (up to Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study. Analysis population was participants in safety analysis set who switched to calcium channel blocker (CCB)-containing ARB combination drug therapy from candesartan therapy at Week 14 and were assessed with this outcome measure.
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description:
Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Participants Analyzed 2666
Mean (Standard Deviation)
Unit of Measure: mmHg
SBP -26.9  (20.54)
DBP -14.7  (13.53)
6.Secondary Outcome
Title Number of Participants Who Experience at Least One Adverse Drug Reactions
Hide Description Adverse drug reactions are defined as adverse events (AEs) which are in the investigator’s opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.
Time Frame Up to Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all participants who were enrolled and completed the study.
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description:
Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
Overall Number of Participants Analyzed 17130
Measure Type: Count of Participants
Unit of Measure: Participants
132
   0.8%
Time Frame Up to Month 3
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants may be represented in more than 1 category.
 
Arm/Group Title Candesartan Cilexetil 4 mg to 8 mg
Hide Arm/Group Description Candesartan cilexetil 4 mg - 8 mg, tablet, orally, once daily. Meanwhile, treatment was to be started at 2 mg once daily in patients with renal impairment and the dose could be increased up to 8 mg as necessary. Participants received interventions as part of routine medical care.
All-Cause Mortality
Candesartan Cilexetil 4 mg to 8 mg
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Candesartan Cilexetil 4 mg to 8 mg
Affected / at Risk (%)
Total   36/17130 (0.21%) 
Blood and lymphatic system disorders   
Disseminated intravascular coagulation  1  1/17130 (0.01%) 
Cardiac disorders   
Bradycardia  1  2/17130 (0.01%) 
Cardiac failure  1  1/17130 (0.01%) 
Cardiac failure chronic  1  1/17130 (0.01%) 
Cardiac tamponade  1  1/17130 (0.01%) 
Eye disorders   
Binocular eye movement disorder  1  1/17130 (0.01%) 
Gastrointestinal disorders   
Abdominal pain  1  1/17130 (0.01%) 
Constipation  1  1/17130 (0.01%) 
Duodenal ulcer  1  1/17130 (0.01%) 
Ileus  1  1/17130 (0.01%) 
Intestinal obstruction  1  1/17130 (0.01%) 
Vomiting  1  1/17130 (0.01%) 
Mechanical ileus  1  1/17130 (0.01%) 
General disorders   
Death  1 [1]  1/17130 (0.01%) 
Pain  1  1/17130 (0.01%) 
Hepatobiliary disorders   
Cholecystitis acute  1  1/17130 (0.01%) 
Infections and infestations   
Pneumonia  1  1/17130 (0.01%) 
Injury, poisoning and procedural complications   
Subdural haematoma  1  1/17130 (0.01%) 
Pelvic fracture  1  1/17130 (0.01%) 
Investigations   
Blood bilirubin increased  1  1/17130 (0.01%) 
Metabolism and nutrition disorders   
Dehydration  1  1/17130 (0.01%) 
Musculoskeletal and connective tissue disorders   
Musculoskeletal stiffness  1  1/17130 (0.01%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Bile duct cancer  1  1/17130 (0.01%) 
Breast cancer recurrent  1  1/17130 (0.01%) 
Gallbladder cancer  1  1/17130 (0.01%) 
Hepatic neoplasm  1  1/17130 (0.01%) 
Papillary tumour of renal pelvis  1  1/17130 (0.01%) 
Uterine cancer  1  1/17130 (0.01%) 
Prostate cancer  1  1/17130 (0.01%) 
Nervous system disorders   
Cerebral infarction  1  2/17130 (0.01%) 
Cervical myelopathy  1  1/17130 (0.01%) 
Subarachnoid haemorrhage  1  1/17130 (0.01%) 
Lacunar infarction  1  2/17130 (0.01%) 
Renal and urinary disorders   
Urinary retention  1  1/17130 (0.01%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1  1/17130 (0.01%) 
Asthma  1  1/17130 (0.01%) 
Pneumonia aspiration  1  1/17130 (0.01%) 
Surgical and medical procedures   
Prostatic operation  1  1/17130 (0.01%) 
Vascular disorders   
Aortic aneurysm rupture  1  1/17130 (0.01%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA/J ver. 16.0
[1]
The reasons of events are not determined because assessment findings were insufficient to specify the reason.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.2%
Candesartan Cilexetil 4 mg to 8 mg
Affected / at Risk (%)
Total   41/17130 (0.24%) 
Nervous system disorders   
Dizziness  1  41/17130 (0.24%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA/J ver. 16.0
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 first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02211638     History of Changes
Other Study ID Numbers: 460-017
JapicCTI-132380 ( Registry Identifier: JapicCTI )
JapicCTI-R171021 ( Other Identifier: JapicCTI )
First Submitted: March 17, 2014
First Posted: August 7, 2014
Results First Submitted: September 1, 2017
Results First Posted: November 5, 2018
Last Update Posted: November 5, 2018