Olmesartan/HCTZ 40/12.5 mg Combination Therapy Versus Olmesartan Medoxomil 40 mg Monotherapy in Essential Hypertension

July 8, 2021 updated by: Menarini Group

Phase III Study Evaluating the Efficacy and Safety of Olmesartan Medoxomil/Hydrochlorothiazide 40/12.5 mg Combination Therapy Versus Olmesartan Medoxomil 40 mg Monotherapy in Patients With Essential Hypertension

The primary objective of this study was to assess the anti-hypertensive effect of OM/HCTZ 40/12.5 mg combination therapy compared to OM 40 mg monotherapy in lowering sitting diastolic BP in hypertensive patients after 8 weeks of double-blind treatment.

The study consisted of two sequential phases of 8 weeks duration each:

During the first phase, OM 40 mg monotherapy was compared with OM/HCTZ 40/12.5 mg in order to evaluate the additional benefit of OM/HCTZ 40/12.5 mg in the treatment of essential moderate to severe hypertension.

During the second phase, patients whose BP proved to be insufficiently controlled by the OM 40 mg monotherapy were to start OM/HCTZ 40/12.5 mg combination therapy while patients whose BP proved to be insufficiently controlled by the OM/HCTZ 40/12.5 mg combination were to be up-titrated to the OM/HCTZ 40/25 mg combination to evaluate the additional benefit of the up-titrated combination.

The study was be conducted by qualified and experienced personnel with adherence to GCP, current guidelines on the design of studies in hypertension, the applicable regulatory requirements and the ethical principles based on the Declaration of Helsinki.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Methodology:

After the signature of the informed consent, patients were screened for eligibility and eligible patients entered into a pre-randomisation period consisting of a taper-off phase of approximately 1-2 weeks (during which patients treated for hypertension were to discontinue their antihypertensive therapy) followed by a 2-week single-blind placebo run-in phase (Visit 1). After conclusion of the placebo run-in phase (Visit 2), eligible patients were randomised to the double-blind active treatment period which consisted of two phases:

First double-blind treatment phase (Phase A, from Randomisation to Week 8):

Eligible patients with mean sitting sBP ≥ 160 and ≤ 200 mmHg and dBP ≥ 100 mmHg and ≤ 120 mmHg were randomised in a 1:2 ratio to receive either OM 40 mg or OM/HCTZ 40/12.5 mg for a total of 8 weeks of treatment (Phase A). Study visits were held after 4 and 8 weeks of double-blind active treatment (Visit 3 and 4, respectively). After 8 weeks (Visit 4), patients reaching the BP goal of < 140/90 mmHg or < 130/80 mmHg for diabetics were considered as responders. All patients (responders and non-responders) then entered into the titration phase of the study (Phase B):

Second double-blind treatment phase/titration phase (Phase B, from Week 8 to Week 16):

Treatment assignment in the second part of the study was based on the following criteria:

  • Responders to Phase A treatment continued to receive the same double-blind treatment for an additional 8 weeks.

  • Non-responders Phase A treatment had their treatment assigned as follows:

    • Non-responders to OM 40 mg were treated with OM/HCTZ 40/12.5 mg for an additional 8 weeks.
    • Non-responders to OM/HCTZ 40/12.5 mg were uptitrated to OM/HCTZ 40/25 mg for an additional 8 weeks. During Phase B of the study, visits were held 12 and 16 weeks after randomisation (Visits 5 and 6, respectively).

The study ended at Visit 6 and a final examination was performed. A safety follow-up (SFU) telephone contact was performed 2 weeks after the end of the treatment. An SFU visit was performed if deemed necessary by the investigator.

Sphygmomanometer was used for BP measurement throughout the trial. BP was measured at all visits as nearly as possible at the same time of the day as trough readings (24 ± 2 h after last drug intake) after a 10 minute rest period. Three separate sitting BP measurements were taken at least 1 minute apart from each other. The 3 results were then averaged and rounded to a whole integer.

Patients with sBP values > 200 mmHg and/or dBP values > 120 mmHg at any time during the study were to be discontinued from the study.

Study Type

Interventional

Enrollment (Actual)

1004

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Rijeka, Croatia
      • Slavonski Brod, Croatia
      • Split, Croatia
      • Varaždin, Croatia
      • Zadar, Croatia
      • Zagreb, Croatia
  • Czechia
      • Benatky nad Jizerou, Czechia
      • Bilovec, Czechia
      • Brodce, Czechia
      • Jablonec nad Nisou, Czechia
      • Mlada Boleslav, Czechia
      • Praha, Czechia
      • Rokycany, Czechia
      • Tabor, Czechia
      • Teplice, Czechia
      • Unicov, Czechia
  • Denmark
      • Aalborg, Denmark
      • Ballerup, Denmark
      • Vejle, Denmark
  • Germany
      • Berlin, Germany
      • Dresden, Germany
      • Einbeck, Germany
      • Essen, Germany
      • Giengen an der Brenz, Germany
      • Großheirath, Germany
      • Hamburg, Germany
      • Hanau, Germany
      • Heidelberg, Germany
      • Köln, Germany
      • Künzing, Germany
      • Leipzig, Germany
      • Lollar, Germany
      • Mannheim, Germany
      • München, Germany
      • Nürnberg, Germany
  • Israel
      • Ashkelon, Israel
      • Beer Sheva, Israel
      • Haifa, Israel
      • Jerusalem, Israel
      • Kfar Saba, Israel
      • Nahariya, Israel
      • Petach Tikva, Israel
      • Tel-Aviv, Israel
      • Tel-Hashomer, Israel
  • Italy
      • Busto Arsizio, Italy
      • Ferrara, Italy
      • Pavia, Italy
      • Pisa, Italy
      • San Daniele del Friuli, Italy
      • Sassari, Italy
      • Somma Lombardo, Italy
      • Venezia, Italy
  • Poland
      • Białystok, Poland
      • Gdańsk, Poland
      • Gdynia, Poland
      • Lublin, Poland
      • Płock, Poland
      • Warszawa, Poland
      • Wąbrzeżno, Poland
  • Romania
      • Baia-Mare, Romania
      • Braila, Romania
      • Bucharest, Romania
      • Cluj, Romania
      • Oradea, Romania
      • Suceava, Romania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with a diagnosis of essential hypertension, either treatment-naive or including currently on anti-hypertensive medication (in Italy only treatment naive patients) in whom it is medically justifiable to withdraw treatment , and who are likely to meet the required BP inclusion criteria at randomisation:

    • Mean sitting dBP ≥ 100 mmHg and ≤ 120 mmHg.
    • Mean sitting sBP ≥ 160 mmHg and ≤ 200 mmHg.

Main Exclusion Criteria:

  • Mean sitting sBP values > 200 mmHg and/or dBP > 120 mmHg.
  • Pregnant or nursing women.
  • Patients with serious disorders which may limit the ability to evaluate the efficacy or safety of the tested medication, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological, oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic patients.
  • Patients with secondary hypertension of any aetiology such as renal disease, pheochromocytoma, or Cushing's syndrome.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: OM 40
Olmesartanmedoxomil (OM)40 mg tablets.
Drug: OM 40
Initially patients were to be treated with Olmesartanmedoxomil (OM)40 mg tablets once daily for 8 weeks. After 8 weeks non-responders were to be uptitrated to OM/HCTZ 40/12.5 mg and responders remained on the previous therapy for further 8 weeks.
Other Names:
  • Treatment
Experimental: OM/HCTZ 40/12.5
Olmesartanmedoxomil (OM) /Hydrochlorothiazide (HCTZ)40/12.5 mg tablets.
Drug: OM/HCTZ 40/12.5
Initially patients were to be treated with Olmesartanmedoxomil (OM) /Hydrochlorothiazide (HCTZ)40/12.5 mg tablets once daily for 8 weeks. After 8 weeks non-responders were to be uptitrated to OM/HCTZ 40/25 mg and responders remained on the previous therapy for further 8 weeks.
Other Names:
  • Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
dBP Change After 8 Weeks Phase A
Time Frame: Eight weeks
Reduction in Mean Trough Sitting dBP (mmHg) from Baseline (Week 0) to Week 8
Eight weeks
sBP Change After 8 Weeks Phase A
Time Frame: Eight weeks
Reduction in Mean Trough Sitting sBP (mmHg) from Baseline (Week 0) to Week 8
Eight weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
dBP Change After 8 Weeks Phase B
Time Frame: Eight weeks
Reduction in trough sitting diastolic blood pressure after 8 weeks of additional treatment, depending on Phase A treatment and outcome (responder/non-responder).
Eight weeks
sBP Change After 8 Weeks Phase B
Time Frame: Eight weeks
Reduction in trough sitting systolic blood pressure after 8 weeks of additional treatment, depending on Phase A treatment and outcome (responder/non-responder).
Eight weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Menarini Group

Collaborators

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Investigators

  • Principal Investigator: Roberto Fogari, MD, Medical Clinic Policlinico San Matteo University of Pavia Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

February 27, 2007

First Submitted That Met QC Criteria

February 27, 2007

First Posted (Estimate)

February 28, 2007

Study Record Updates

Last Update Posted (Actual)

July 28, 2021

Last Update Submitted That Met QC Criteria

July 8, 2021

Last Verified

June 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CS866CM-B-E303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe