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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02211638
• Collaborator: (none)
• Enrollment: 18,113
• Location: 1
• Actual Duration (Months): 22.4
• Patients Per Site Per Month: 808.4

Study Details

Study Description

Brief Summary

The purpose of this study is to gain an understanding of the actual use of candesartan cilexetil (Blopress) in patients with hypertension, and to examine the changes in parameters such as blood pressure.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Candesartan Cilexetil

Detailed Description

This special drug use surveillance was planned to gain an understanding of the actual use of candesartan cilexetil in the new anti-hypertensive treatment environment where angiotensin receptor blocker (ARB) combination drugs have become commercially available. The surveillance also investigated the background factors of patients continuing treatment with candesartan cilexetil and patients who switched from candesartan cilexetil to ARB combination drugs, as well as changes in parameters such as blood pressure.

The usual adult dosage of Candesartan cilexetil is 4 to 8 mg, administered 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.

Study Design

• Study Type: Observational
• Actual Enrollment: 18113 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Blopress Tablets Special Drug Use Surveillance 「Challenge - Quality Control」
• Actual Study Start Date: Jun 13, 2011
• Actual Primary Completion Date: Apr 25, 2013
• Actual Study Completion Date: Apr 25, 2013

Arms and Interventions

Arm	Intervention/Treatment
Candesartan Cilexetil tablets (2 to 12 mg) Candesartan Cilexetil tablets (2 to 12 mg), orally, once daily for up to 3 months	Drug: Candesartan Cilexetil; Candesartan Cilexetil tablet; Other Names: Blopress

Outcome Measures

Primary Outcome Measures

1. Changes in Clinic Blood Pressure in the Sitting Position [Baseline, Month 3 and Last dose of Candesartan (up to Month 6)]

   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.

2. Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Continued Candesartan Therapy at Week 14 [Baseline, Month 3 and Last dose of Candesartan (up to Month 6)]

   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.

3. Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Switched to ARB Combination Drug Therapy at Week 14 [Baseline, Month 3, Last dose of Candesartan, and Last dose of ARB Combination Drug (up to Month 6)]

   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.

4. Changes in Clinic Blood Pressure in the Sitting Position for Participants Who Switched to Diuretic-containing ARB Combination Drug Therapy at Week 14 [Baseline and Last dose of ARB Combination Drug (up to Month 6)]

   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.

5. 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 [Baseline and Last dose of ARB Combination Drug (up to Month 6)]

   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.

Secondary Outcome Measures

1. Number of Participants Who Experience at Least One Adverse Drug Reactions [Up to Month 3]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hypertensive patients

Exclusion Criteria:

1. Inpatients

2. Patients under dialysis (planned)

3. Patients with a history of coronary artery disease/cerebrovascular disorder within 6 months

4. Patients with ≥ class III of the New York Heart Association (NYHA) classification functional classification of heart failure

5. Patients that have been prescribed with candesartan (this drug/Ecard/Unisia) in the past

6. Patients who are pregnant or may possibly become pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Osaka		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02211638
• Other Study ID Numbers: 460-017; JapicCTI-132380; JapicCTI-R171021
• First Posted: Aug 7, 2014
• Last Update Posted: Nov 5, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug Therapy
• Additional relevant MeSH terms: Hypertension; Candesartan; Candesartan cilexetil

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1503 investigative sites in Japan, from 13-Jun-2011 to 25-Apr-2013.
Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	Candesartan Cilexetil 4 mg to 8 mg
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 Participants	17130
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.9 (12.85)
Sex: Female, Male (Count of Participants)
Female	8640 50.4%
Male	8490 49.6%
Region of Enrollment (Number) [Number]
Japan	17130 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	61.3 (13.46)
Smoking Classification (Count of Participants)
Never Smoked	11683 68.2%
Current Smoker	2032 11.9%
Unknown	3415 19.9%
Medical Complications (Count of Participants)
Had no Medical Complications	7988 46.6%
Had Medical Complications	9142 53.4%
Medical History (Count of Participants)
Had no Medical History	14376 83.9%
Had Medical History	2754 16.1%
Initial Dose of Study Drug (Count of 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 (Count of Participants)
Had no Concomitant Antihypertensive Drugs	11968 69.9%
Had Concomitant Antihypertensive Drugs	5162 30.1%
Switching Antihypertensive Drugs (Count of Participants)
Had no Switching Antihypertensive Drugs	12856 75%
Had Switching Antihypertensive Drugs	4274 25%
Status of Administration of Antihypertensive Drugs (Count of Participants)
Had no Antihypertensive Drugs	10055 58.7%
Had Antihypertensive Drugs	7075 41.3%
Clinical Systolic Blood Pressure (SBP) (Sitting) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	156.1 (18.67)
Clinical Diastolic Blood Pressure (DBP) (Sitting) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	88.7 (13.47)
Early Morning Home SBP (Ave) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	153.9 (15.89)
Early Morning Home DBP (Ave) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	89.4 (11.41)
Evening Home SBP (Ave) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	146.2 (15.88)
Evening Home DBP (Ave) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	85.5 (11.59)
Spot Urine Sodium: NaS (mEq/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mEq/L]	129.9 (52.78)
Spot Urine Creatinine: CrS (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	804.2 (1002.82)
Estimated 24hr Creatinine Excretion: UCr24 (mg/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/day]	1099.52 (349.732)
Estimated 24hr Sodium Excretion: UNa24 (mEq/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mEq/day]	230.70 (246.267)
Salt Intake: NaCl24 (g/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/day]	13.5 (14.41)
Salt Intake: NaCl24 (g/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/day]	10.0 (2.92)
Focus on Blood Pressure (BP) Measurement (Count of 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%

Outcome Measures

1. Primary Outcome

Title	Changes in Clinic Blood Pressure in the Sitting Position
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)

Outcome Measure Data

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
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.
Measure Participants	16617
Month 3, SBP	-20.1 (19.30)
Last Dose of Candesartan, SBP	-18.1 (18.91)
Month 3, DBP	-10.4 (12.34)
Last Dose of Candesartan, DBP	-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
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)

Outcome Measure Data

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
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.
Measure Participants	11753
Month 3, SBP	-19.8 (18.74)
Last Dose of Candesartan, SBP	-19.5 (18.64)
Month 3, DBP	-10.1 (12.01)
Last Dose of Candesartan, DBP	-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
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)

Outcome Measure Data

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
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.
Measure Participants	3630
Month 3, SBP	-21.7 (20.74)
Last Dose of Candesartan, SBP	-12.3 (18.83)
Last dose of ARB Combination Drug, SBP	-26.4 (20.49)
Month 3, DBP	-11.8 (13.26)
Last Dose of Candesartan, DBP	-6.4 (12.04)
Last dose of ARB Combination Drug, DBP	-14.4 (13.45)

4. Secondary Outcome

Title	Number of Participants Who Experience at Least One Adverse Drug Reactions
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

Outcome Measure Data

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
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.
Measure Participants	17130
Count of Participants [Participants]	132 0.8%

5. 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
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)

Outcome Measure Data

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
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.
Measure Participants	984
SBP	-24.5 (20.20)
DBP	-13.2 (13.62)

6. 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
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)

Outcome Measure Data

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
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.
Measure Participants	2666
SBP	-26.9 (20.54)
DBP	-14.7 (13.53)

Adverse Events

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
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Candesartan Cilexetil 4 mg to 8 mg
	Affected / at Risk (%)	# Events
Total	36/17130 (0.2%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/17130 (0%)
Cardiac disorders
Bradycardia	2/17130 (0%)
Cardiac failure	1/17130 (0%)
Cardiac failure chronic	1/17130 (0%)
Cardiac tamponade	1/17130 (0%)
Eye disorders
Binocular eye movement disorder	1/17130 (0%)
Gastrointestinal disorders
Abdominal pain	1/17130 (0%)
Constipation	1/17130 (0%)
Duodenal ulcer	1/17130 (0%)
Ileus	1/17130 (0%)
Intestinal obstruction	1/17130 (0%)
Vomiting	1/17130 (0%)
Mechanical ileus	1/17130 (0%)
General disorders
Death	1/17130 (0%)
Pain	1/17130 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/17130 (0%)
Infections and infestations
Pneumonia	1/17130 (0%)
Injury, poisoning and procedural complications
Subdural haematoma	1/17130 (0%)
Pelvic fracture	1/17130 (0%)
Investigations
Blood bilirubin increased	1/17130 (0%)
Metabolism and nutrition disorders
Dehydration	1/17130 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	1/17130 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer	1/17130 (0%)
Breast cancer recurrent	1/17130 (0%)
Gallbladder cancer	1/17130 (0%)
Hepatic neoplasm	1/17130 (0%)
Papillary tumour of renal pelvis	1/17130 (0%)
Uterine cancer	1/17130 (0%)
Prostate cancer	1/17130 (0%)
Nervous system disorders
Cerebral infarction	2/17130 (0%)
Cervical myelopathy	1/17130 (0%)
Subarachnoid haemorrhage	1/17130 (0%)
Lacunar infarction	2/17130 (0%)
Renal and urinary disorders
Urinary retention	1/17130 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/17130 (0%)
Asthma	1/17130 (0%)
Pneumonia aspiration	1/17130 (0%)
Surgical and medical procedures
Prostatic operation	1/17130 (0%)
Vascular disorders
Aortic aneurysm rupture	1/17130 (0%)
Other (Not Including Serious) Adverse Events
	Candesartan Cilexetil 4 mg to 8 mg
	Affected / at Risk (%)	# Events
Total	41/17130 (0.2%)
Nervous system disorders
Dizziness	41/17130 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.