Trial Outcomes & Findings for Candesartan Cilexetil / Hydrochlorothiazide Combination Tablets Special Drug Use Surveillance: Long-term Use (12 Months) (NCT NCT02016183)

NCT ID: NCT02016183

Last Updated: 2018-11-09

Results Overview

ADRs 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.

Recruitment status

COMPLETED

Target enrollment

3222 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2018-11-09

Participant Flow

Participants took part in the study at 557 investigative sites in Japan, from 01-Apr-2009 to 30-Sep-2012.

Participants with a diagnosis of hypertension were enrolled to receive candesartan cilexetil/hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months as per routine medical practice.

Participant milestones

Participant milestones
Measure	Candesartan Cilexetil/Hydrochlorothiazide Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Overall Study STARTED	3222
Overall Study COMPLETED	3157
Overall Study NOT COMPLETED	65

Reasons for withdrawal

Reasons for withdrawal
Measure	Candesartan Cilexetil/Hydrochlorothiazide Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Overall Study Case Report Forms Uncollected	13
Overall Study Protocol Violation	52

Baseline Characteristics

Candesartan Cilexetil / Hydrochlorothiazide Combination Tablets Special Drug Use Surveillance: Long-term Use (12 Months)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=3157 Participants Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Age, Continuous	69.6 Years STANDARD_DEVIATION 12.27 • n=5 Participants
Sex: Female, Male Female	1746 Participants n=5 Participants
Sex: Female, Male Male	1411 Participants n=5 Participants
Region of Enrollment Japan	3157 Participants n=5 Participants
Healthcare Category Outpatient	3065 Participants n=5 Participants
Healthcare Category Inpatient	18 Participants n=5 Participants
Healthcare Category Inpatient and outpatient	74 Participants n=5 Participants
BMI	24.61 kg/m^2 STANDARD_DEVIATION 3.885 • n=5 Participants
Waist Circumference	87.21 cm STANDARD_DEVIATION 10.458 • n=5 Participants
Smoking Classification Never smoked	2332 Participants n=5 Participants
Smoking Classification Current/Ex smoker	409 Participants n=5 Participants
Smoking Classification Unknown	416 Participants n=5 Participants
Allergy/Predisposition to Hypersensitivity Had no Allergy/Predisposition to Hypersensitivity	2811 Participants n=5 Participants
Allergy/Predisposition to Hypersensitivity Had Allergy/Predisposition to Hypersensitivity	345 Participants n=5 Participants
Allergy/Predisposition to Hypersensitivity Unknown	1 Participants n=5 Participants
Medical Complications Had no Medical Complications	798 Participants n=5 Participants
Medical Complications Had Medical Complications	2359 Participants n=5 Participants
Medical History Had no Medical History	2603 Participants n=5 Participants
Medical History Had Medical History	552 Participants n=5 Participants
Medical History Unknown	2 Participants n=5 Participants
Duration of Disease	7.12 Years STANDARD_DEVIATION 7.289 • n=5 Participants
Use of Antihypertensive Drug Prior to the Start of the Study Drug Had Not Used Antihypertensive Drug	185 Participants n=5 Participants
Use of Antihypertensive Drug Prior to the Start of the Study Drug Had Used Antihypertensive Drug	2972 Participants n=5 Participants
Violation of Inclusion or Exclusion Criteria Had No Violation	3154 Participants n=5 Participants
Violation of Inclusion or Exclusion Criteria Had Any Violation	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: The safety analysis set was defined as all participants who were enrolled and completed the study.

Outcome measures

Outcome measures
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=3157 Participants Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs)	283 Participants

SECONDARY outcome

Timeframe: Baseline, and Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and Final assessment (up to 12 months)

Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points. Here 'n' is number of participants analyzed at the given time point.

Reported data are changes in SBP from baseline at Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and final assessment.

Outcome measures

Outcome measures
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=3072 Participants Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 1	-13.3 mmHg Standard Deviation 18.02
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 2	-14.8 mmHg Standard Deviation 18.48
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 3	-15.4 mmHg Standard Deviation 19.06
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 4	-15.7 mmHg Standard Deviation 19.34
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 5	-15.6 mmHg Standard Deviation 19.17
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 6	-16.1 mmHg Standard Deviation 18.94
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 7	-15.8 mmHg Standard Deviation 19.27
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 8	-15.8 mmHg Standard Deviation 19.12
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 9	-16.4 mmHg Standard Deviation 18.86
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 10	-16.6 mmHg Standard Deviation 18.60
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 11	-17.0 mmHg Standard Deviation 18.88
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Month 12	-18.1 mmHg Standard Deviation 18.86
Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point Change in SBP at Final	-17.5 mmHg Standard Deviation 19.87

SECONDARY outcome

Timeframe: Baseline, and Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and Final assessment (up to 12 months)

Reported data are changes in DBP from baseline at Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and final assessment.

Outcome measures

Outcome measures
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=3072 Participants Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 1	-6.5 mmHg Standard Deviation 11.40
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 2	-7.3 mmHg Standard Deviation 11.52
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 3	-7.6 mmHg Standard Deviation 11.93
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 4	-7.8 mmHg Standard Deviation 11.97
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 5	-7.8 mmHg Standard Deviation 12.01
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 6	-8.0 mmHg Standard Deviation 12.12
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 7	-8.1 mmHg Standard Deviation 12.42
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 8	-8.2 mmHg Standard Deviation 12.32
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 9	-8.5 mmHg Standard Deviation 12.26
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 10	-8.7 mmHg Standard Deviation 12.49
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 11	-8.5 mmHg Standard Deviation 12.37
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Month 12	-9.1 mmHg Standard Deviation 12.23
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point Change in DBP at Final	-8.5 mmHg Standard Deviation 12.59

SECONDARY outcome

Timeframe: Baseline, and Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and Final assessment (up to 12 months)

Reported data are changes in Pulse Rate from baseline at Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and final assessment.

Outcome measures

Outcome measures
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=2120 Participants Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Final assessment	-1.6 Beats per minutes Standard Deviation 10.86
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 1	-1.3 Beats per minutes Standard Deviation 9.16
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 2	-1.1 Beats per minutes Standard Deviation 9.76
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 3	-1.3 Beats per minutes Standard Deviation 9.40
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 4	-1.5 Beats per minutes Standard Deviation 9.91
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 5	-1.3 Beats per minutes Standard Deviation 9.99
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 6	-1.5 Beats per minutes Standard Deviation 10.23
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 7	-1.1 Beats per minutes Standard Deviation 10.45
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 8	-1.5 Beats per minutes Standard Deviation 10.08
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 9	-1.6 Beats per minutes Standard Deviation 10.37
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 10	-1.7 Beats per minutes Standard Deviation 10.58
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 11	-1.5 Beats per minutes Standard Deviation 10.56
Changes From Baseline in Pulse Rate at Each Time Point Change in Pulse Rate at Month 12	-1.8 Beats per minutes Standard Deviation 10.35

Adverse Events

Candesartan Cilexetil/Hydrochlorothiazide

Serious events: 72 serious events

Other events: 158 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=3157 participants at risk Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Infections and infestations Bronchopneumonia	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Infections and infestations Pharyngitis	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Infections and infestations Pneumonia	0.16% 5/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Infections and infestations Pyelonephritis acute	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Infections and infestations Urinary tract infection	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Infections and infestations Pneumonia bacterial	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Infections and infestations Atypical mycobacterial infection	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute monocytic leukaemia	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.10% 3/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Metabolism and nutrition disorders Diabetes mellitus	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Metabolism and nutrition disorders Hyperkalaemia	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Metabolism and nutrition disorders Hyponatraemia	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Metabolism and nutrition disorders Hypophagia	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Psychiatric disorders Completed suicide	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Brain stem infarction	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Cerebral haemorrhage	0.10% 3/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Cerebral infarction	0.16% 5/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Convulsion	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Loss of consciousness	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Transient ischaemic attack	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Nervous system disorders Cerebral artery stenosis	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Ear and labyrinth disorders Vertigo	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Acute myocardial infarction	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Angina pectoris	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Atrial fibrillation	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Cardiac failure	0.13% 4/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Cardiac failure acute	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Cardiac failure chronic	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Myocardial infarction	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Cardiac disorders Acute coronary syndrome	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Vascular disorders Hypertension	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Vascular disorders Hypotension	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Gastrointestinal disorders Gastric ulcer	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Gastrointestinal disorders Ileus	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Gastrointestinal disorders Melaena	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Musculoskeletal and connective tissue disorders Back pain	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Renal and urinary disorders Renal disorder	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Renal and urinary disorders Renal failure acute	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Renal and urinary disorders Renal failure chronic	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Renal and urinary disorders Urinary retention	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Renal and urinary disorders Diabetic nephropathy	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Renal and urinary disorders Renal impairment	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
General disorders Chest discomfort	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
General disorders Death	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
General disorders Oedema peripheral	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
General disorders Sudden death	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Investigations Blood creatinine increased	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Investigations Blood urea increased	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Injury, poisoning and procedural complications Compression fracture	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Injury, poisoning and procedural complications Fall	0.13% 4/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Injury, poisoning and procedural complications Fracture	0.06% 2/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Injury, poisoning and procedural complications Subdural haematoma	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Injury, poisoning and procedural complications Tendon rupture	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Injury, poisoning and procedural complications Heat illness	0.03% 1/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.

Other adverse events

Other adverse events
Measure	Candesartan Cilexetil/Hydrochlorothiazide n=3157 participants at risk Candesartan cilexetil/Hydrochlorothiazide 4 mg/6.25 mg or 8 mg/6.25 mg combination tablets, orally, once daily for up to 12 months. This drug should not be used as a first-line drug for hypertension treatment. Participants received interventions as part of routine medical care.
Metabolism and nutrition disorders Hyperuricaemia	2.6% 81/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.
Investigations Blood uric acid increased	2.4% 77/3157 • Up to 12 months At each visit the investigator had to document any occurrence of AEs 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.

Additional Information

Medical Director

Takeda

Phone: 1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER