Clinical trial NCT00902538: Hydrochlorothiazide as add-on to Olmesartan/Amlodipine in Hypertension
Official title: Add-on Study of Hydrochlorothiazide in Patients With Moderate to Severe Hypertension Not Achieving Target Blood Pressure on Olmesartan/Amlodipine Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Essential Hypertension
Keywords: Add on treatment
essential hypertension
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2009-05-15
Enrollment: 2204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: 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
timeFrame: baseline (8 weeks) to 16 weeks
Secondary outcomes:
measure: 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
timeFrame: baseline (8 weeks) to week 16
measure: Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16.
timeFrame: baseline (week 8) to week 16
measure: Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM).
timeFrame: Baseline (8 weeks) to 16 weeks
measure: Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
timeFrame: Baseline (8 weeks) to 16 weeks
measure: 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.
timeFrame: week 24 to week 32
measure: In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg.
timeFrame: week 24 to week 32
measure: In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg.
timeFrame: week 24 to week 32
measure: In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
timeFrame: Week 16 to week 32
measure: In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
timeFrame: Week 16 to week 32
Other outcomes:
Locations:
city: Graz
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Antwerpen
country: Belgium
city: Lauwe
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Massemen
country: Belgium
city: Oostham
country: Belgium
city: Haskovo
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Bilovec
country: Czechia
city: Brno
country: Czechia
city: Havlickuv Brod
country: Czechia
city: Hodonin
country: Czechia
city: Kladno
country: Czechia
city: Kolin
country: Czechia
city: Ostrava-Vitkovice
country: Czechia
city: Ostrava
country: Czechia
city: Praha
country: Czechia
city: Copenhagen
country: Denmark
city: Frederiksberg
country: Denmark
city: Naestved
country: Denmark
city: Roskilde
country: Denmark
city: Albi
country: France
city: Angers
country: France
city: Brest
country: France
city: Cambrai
country: France
city: Creteil
country: France
city: Dijon
country: France
city: Dinard
country: France
city: Lyon
country: France
city: Nancy
country: France
city: Pessac
country: France
city: Roubaix
country: France
city: Strasbourg
country: France
city: Tierce
country: France
city: Vandoeuvre
country: France
city: Villefranche de Rouergue
country: France
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Einbeck
country: Germany
city: Hamburg
country: Germany
city: Magdeburg
country: Germany
city: Muenchen
country: Germany
city: Strasskirchen
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Wermsdorf
country: Germany
city: Almere
country: Netherlands
city: Beek en Donk
country: Netherlands
city: Doetinchem
country: Netherlands
city: Groningen
country: Netherlands
city: Losser
country: Netherlands
city: Maastricht
country: Netherlands
city: Bytom
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Piotrkow Trybunalski
country: Poland
city: Pulawy
country: Poland
city: Siemianowice Slaskie
country: Poland
city: Tarnow
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Oradea
country: Romania
city: Pitesti
country: Romania
city: Targoviste
country: Romania
city: Targu Mures
country: Romania
city: Timisoara
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Banska Bysterica
country: Slovakia
city: Brastislava
country: Slovakia
city: Dolny Kubin
country: Slovakia
city: Kosice
country: Slovakia
city: Presov
country: Slovakia
city: Sahy
country: Slovakia
city: La Gineta
country: Spain
state: Albacete
city: La Roda
country: Spain
state: Albacete
city: Port De Sagunt
country: Spain
state: Valencia
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Elche
country: Spain
city: Granada
country: Spain
city: Madrid
country: Spain
city: Palma de Mallorca
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Vizcaya
country: Spain
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Mykolayiv
country: Ukraine
city: Odesa
country: Ukraine
city: Simferopol
country: Ukraine
city: Uzhorod
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Yalta
country: Ukraine
Study officials:
References: