Hydrochlorothiazide as add-on to Olmesartan/Amlodipine in Hypertension
Add-on Study of Hydrochlorothiazide in Patients With Moderate to Severe Hypertension Not Achieving Target Blood Pressure on Olmesartan/Amlodipine Alone
1 other identifier
interventional
2,204
14 countries
117
Brief Summary
Both Olmesartan (OLM)/Amlodipine (AML) combination and Hydrochlorothiazide (HCTZ) have proven to be efficacious and safe in lowering blood pressure, but may not always be sufficient. This study is to test efficacy and safety of the combination of OLM/AML and HCTZ in hypertensive patients whose blood pressure is not adequately controlled with OLM/AML alone. The following treatments will be included in the trial: OLM 40mg/AML 10mg; OLM 40mg/AML 10 mg/HCTZ 12.5 mg; OLM 40 mg/AML 10 mg/HCTZ 25 mg. The trial has four periods. The treatments that will be used are as follows: Period 1 - OLM 40mg/AML 10mg; Period 2 - OLM 40mg/AML 10mg or OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg; Period 3 - OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 non-responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2009
117 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2009
CompletedFirst Submitted
Initial submission to the registry
May 13, 2009
CompletedFirst Posted
Study publicly available on registry
May 15, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2010
CompletedResults Posted
Study results publicly available
November 22, 2011
CompletedJanuary 11, 2019
February 1, 2012
1.4 years
May 13, 2009
September 6, 2011
December 20, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg
Three cuff blood pressure measurements were taken at each visit.
baseline (8 weeks) to 16 weeks
Secondary Outcomes (9)
Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg
baseline (8 weeks) to week 16
Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16.
baseline (week 8) to week 16
Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM).
Baseline (8 weeks) to 16 weeks
Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
Baseline (8 weeks) to 16 weeks
In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg.
week 24 to week 32
- +4 more secondary outcomes
Study Arms (6)
Olmesartan (OLM) 40mg-Amlodipine (AML) 10mg
EXPERIMENTALThe participants in this arm received these 2 drugs for the 8-week, single-blind, run-in Period 1. Participants could then randomized to this same combination for an additional 8 weeks in the double-blind, Period 2.
Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg
EXPERIMENTALParticipants could start receiving this combination in randomized, double-blind, 8-week Period 2. This combination was continued into single-blind, 8-week Period 3 for all participants entering Period 3.
Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg
EXPERIMENTALParticipants could start receiving this combination in randomized, double-blind, 8- week Period 2.
OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg (Responders)
EXPERIMENTALParticipants who meet their blood pressure goals in Period 3 and continued into the 8-week, double-blind Period 4 continued to receive this combination.
OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg (Non-responders)
EXPERIMENTALParticipants finishing Period 3, but, who did not meet their blood pressure goals could receive this combination in the double-blind, randomized, Period 4
OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg (Non-responders)
EXPERIMENTALParticipants finishing Period 3, but, who did not meet their blood pressure goals could receive this combination in the double-blind, randomized, Period 4
Interventions
Oral tablets containing Olmesartan medoxomil-Amlodipine 40-10 mg, given once daily
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablets. All tablets are given once a day.
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablet. All tablets are given once a day.
Eligibility Criteria
You may qualify if:
- Male or female aged 18 years or older.
- Mean trough seated systolic blood pressure (SeSBP) of ≥ 160/100 mmHg (SeSBP of ≥ 160 mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at screening if not currently on antihypertensive medication (e.g. newly diagnosed subjects)
- OR:
- For subjects on monotherapy: mean trough SeSBP of ≥ 150/95 mmHg (SeSBP of ≥ 150 mmHg and SeDBP ≥ 95 mmHg) at screening
- OR:
- For subjects on any combination of antihypertensive medications that includes either hydrochlorothiazide or amlodipine or olmesartan for a duration of at least four weeks: mean trough SeSBP of ≥ 140/90 mmHg (SeSBP of ≥ 140 mmHg and SeDBP ≥ 90 mmHg) at screening
- OR:
- For subjects on any other combination of antihypertensive medications that includes neither hydrochlorothiazide, amlodipine nor olmesartan: mean trough SeSBP ≥ 160 mmHg, mean trough SeDBP ≥ 100mmHg, at the end of the taper-off period
- Subject freely signs the Informed Consent Form (ICF) after the nature of the study and the disclosure of his/her data has been explained.
- Female subjects of childbearing potential must be using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study \[Visit 1\]). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable), and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If a female becomes pregnant during the study, she has to be withdrawn immediately.
You may not qualify if:
- Female subjects of childbearing potential who are pregnant or lactating.
- Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of the investigational products, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic subjects.
- Subjects having a history of the following within the last six months: myocardial infarction (MI), unstable angina pectoris, percutaneous coronary intervention, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischaemic attack.
- Subjects with clinically significant abnormal laboratory values at Screening, including subjects with one or more of the following:
- Aspartate aminotransferase (AST) \> 3 times upper limit of normal (ULN)
- Alanine aminotransferase (ALT) \> 3 times ULN
- Gamma-glutamyltransferase (GGT) \> 3 times ULN
- Potassium above ULN (unless high value is due to haemolytic blood sample)
- Subjects with secondary hypertension of any aetiology such as renal disease, phaeochromocytoma, or Cushing's syndrome.
- Subjects with contraindication to olmesartan, amlodipine, hydrochlorothiazide, or any of the excipients.
- Subjects with a mean SeSBP \> 200 mmHg or mean SeDBP \> 115 mmHg or bradycardia (heart rate \< 50 beats/min at rest documented by mean radial pulse rate \[PR\] or electrocardiogram \[ECG\]) at Screening (Visit 1) or immediately before taking Period I study medication (Visit 2).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Daiichi Sankyolead
Study Sites (117)
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Graz, Austria
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Salzburg, Austria
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Vienna, Austria
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Antwerp, Belgium
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Lauwe, Belgium
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Leuven, Belgium
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Liège, Belgium
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Massemen, Belgium
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Oostham, Belgium
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Haskovo, Bulgaria
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Pleven, Bulgaria
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Plovdiv, Bulgaria
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Sofia, Bulgaria
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Varna, Bulgaria
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Bílovec, Czechia
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Brno, Czechia
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Havlíčkův Brod, Czechia
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Hodonín, Czechia
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Kladno, Czechia
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Kolín, Czechia
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Ostrava, Czechia
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Ostrava-Vitkovice, Czechia
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Prague, Czechia
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Copenhagen, Denmark
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Frederiksberg, Denmark
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Næstved, Denmark
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Roskilde, Denmark
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Albi, France
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Angers, France
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Brest, France
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Cambrai, France
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Créteil, France
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Dijon, France
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Dinard, France
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Lyon, France
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Nancy, France
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Pessac, France
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Roubaix, France
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Strasbourg, France
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Tiercé, France
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Vandœuvre-lès-Nancy, France
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Villefranche-de-Rouergue, France
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Berlin, Germany
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Dresden, Germany
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Einbeck, Germany
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Hamburg, Germany
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Magdeburg, Germany
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München, Germany
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Straßkirchen, Germany
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Villingen-Schwenningen, Germany
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Wermsdorf, Germany
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Almere Stad, Netherlands
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Beek en Donk, Netherlands
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Doetinchem, Netherlands
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Groningen, Netherlands
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Losser, Netherlands
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Maastricht, Netherlands
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Bytom, Poland
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Gdansk, Poland
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Katowice, Poland
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Krakow, Poland
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Piotrkow Trybunalski, Poland
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Puławy, Poland
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Siemianowice Śląskie, Poland
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Tarnów, Poland
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Torun, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Brasov, Romania
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Bucharest, Romania
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Cluj-Napoca, Romania
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Iași, Romania
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Oradea, Romania
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Piteşti, Romania
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Târgovişte, Romania
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Târgu Mureş, Romania
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Timișoara, Romania
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Moscow, Russia
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Novosibirsk, Russia
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Orenburg, Russia
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Ryazan, Russia
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Saint Petersburg, Russia
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Saratov, Russia
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Smolensk, Russia
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Tomsk, Russia
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Yaroslavl, Russia
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Yekaterinburg, Russia
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Banska Bysterica, Slovakia
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Brastislava, Slovakia
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Dolný Kubín, Slovakia
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Košice, Slovakia
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Prešov, Slovakia
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Šahy, Slovakia
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La Gineta, Albacete, Spain
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La Roda, Albacete, Spain
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Port de Sagunt, Valencia, Spain
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Alicante, Spain
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Barcelona, Spain
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Elche, Spain
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Granada, Spain
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Madrid, Spain
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Palma de Mallorca, Spain
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Seville, Spain
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Valencia, Spain
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Vizcaya, Spain
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Dnipropetrovsk, Ukraine
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Donetsk, Ukraine
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Ivano-Frankivsk, Ukraine
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Kharkiv, Ukraine
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Kiev, Ukraine
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Lviv, Ukraine
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Mykolayiv, Ukraine
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Odesa, Ukraine
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Simferopol, Ukraine
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Uzhhorod, Ukraine
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Vinnytsia, Ukraine
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Yalta, Ukraine
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bettina Ammentorp
- Organization
- Daiichi Sankyo Europe GmbH
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2009
First Posted
May 15, 2009
Study Start
April 1, 2009
Primary Completion
September 1, 2010
Study Completion
October 1, 2010
Last Updated
January 11, 2019
Results First Posted
November 22, 2011
Record last verified: 2012-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
- Access Criteria
- Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/