Hypertension
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the safety and efficacy of long-term use of candesartan cilexetil / hydrochlorothiazide combination tablets (ECARD) Combination Tablets LD&HD in hypertensive patients in the routine clinical setting
Detailed description
This is a special drug use surveillance on long-term use of candesartan cilexetil / hydrochlorothiazide combination tablets (ECARD combination tablets) to evaluate in hypertensive patients in the routine clinical setting. Because the drug contains a diuretic (hydrochlorothiazide) , it is necessary to assess the safety, especially on serum uric acid. (the planned sample size is 3000). The usual adult dosage is 1 tablet (4 mg/6.25 mg or 8 mg/6.25 mg as a candesartan cilexetil/hydrochlorothiazide) administered orally once daily. This drug should not be used as a first-line drug for hypertension treatment.
Interventions
DRUGCandesartan cilexetil / hydrochlorothiazide
Candesartan cilexetil / hydrochlorothiazide combination tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Hypertensive patients
Exclusion criteria
(1) Patients with a history of hypersensitivity to ingredients of ECARD LD&HD combination tablets, thiazides, or their analogues (e.g. sulphonamide derivatives such as chlortalidone) (2) Patients with anuria or patients under hemodialysis (3) Patients with acute renal failure (4) Patients with noticeably decreased Na and K levels in body fluids (5) Pregnant women or women planning to become pregnant \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs) | Up to 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point | 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 SBP from baseline at Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and final assessment. |
| Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point | 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. |
| Changes From Baseline in Pulse Rate at Each Time Point | 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. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 557 investigative sites in Japan, from 01-Apr-2009 to 30-Sep-2012.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3,157 |
| Total | 3,157 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case Report Forms Uncollected | 13 |
| Overall Study | Protocol Violation | 52 |
Baseline characteristics
| Characteristic | Candesartan Cilexetil/Hydrochlorothiazide |
|---|---|
| Age, Continuous | 69.6 Years STANDARD_DEVIATION 12.27 |
| Allergy/Predisposition to Hypersensitivity Had Allergy/Predisposition to Hypersensitivity | 345 Participants |
| Allergy/Predisposition to Hypersensitivity Had no Allergy/Predisposition to Hypersensitivity | 2811 Participants |
| Allergy/Predisposition to Hypersensitivity Unknown | 1 Participants |
| BMI | 24.61 kg/m^2 STANDARD_DEVIATION 3.885 |
| Duration of Disease | 7.12 Years STANDARD_DEVIATION 7.289 |
| Healthcare Category Inpatient | 18 Participants |
| Healthcare Category Inpatient and outpatient | 74 Participants |
| Healthcare Category Outpatient | 3065 Participants |
| Medical Complications Had Medical Complications | 2359 Participants |
| Medical Complications Had no Medical Complications | 798 Participants |
| Medical History Had Medical History | 552 Participants |
| Medical History Had no Medical History | 2603 Participants |
| Medical History Unknown | 2 Participants |
| Region of Enrollment Japan | 3157 Participants |
| Sex: Female, Male Female | 1746 Participants |
| Sex: Female, Male Male | 1411 Participants |
| Smoking Classification Current/Ex smoker | 409 Participants |
| Smoking Classification Never smoked | 2332 Participants |
| Smoking Classification Unknown | 416 Participants |
| Use of Antihypertensive Drug Prior to the Start of the Study Drug Had Not Used Antihypertensive Drug | 185 Participants |
| Use of Antihypertensive Drug Prior to the Start of the Study Drug Had Used Antihypertensive Drug | 2972 Participants |
| Violation of Inclusion or Exclusion Criteria Had Any Violation | 3 Participants |
| Violation of Inclusion or Exclusion Criteria Had No Violation | 3154 Participants |
| Waist Circumference | 87.21 cm STANDARD_DEVIATION 10.458 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 158 / 3,157 |
| serious Total, serious adverse events | 72 / 3,157 |
Outcome results
Primary
Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs)
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.
Time frame: Up to 12 months
Population: The safety analysis set was defined as all participants who were enrolled and completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Candesartan Cilexetil/Hydrochlorothiazide | Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs) | 283 Participants |
Secondary
Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | Changes From Baseline in Diastolic Blood Pressure (DBP) at Each Time Point | Change in DBP at Month 1 | -6.5 mmHg | Standard Deviation 11.4 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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
Changes From Baseline in Pulse Rate at Each Time Point
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | Changes From Baseline in Pulse Rate at Each Time Point | Change in Pulse Rate at Month 3 | -1.3 Beats per minutes | Standard Deviation 9.4 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
Secondary
Changes From Baseline in Systolic Blood Pressure (SBP) at Each 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point | Change in SBP at Month 10 | -16.6 mmHg | Standard Deviation 18.6 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | 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 |
| Candesartan Cilexetil/Hydrochlorothiazide | Changes From Baseline in Systolic Blood Pressure (SBP) at Each Time Point | Change in SBP at Final | -17.5 mmHg | Standard Deviation 19.87 |