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

NCT ID: NCT00441350

Last Updated: 2021-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1004 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2008-05-31

Brief Summary

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.

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

OM 40

Olmesartanmedoxomil (OM)40 mg tablets.

Group Type: ACTIVE_COMPARATOR

OM 40

Intervention Type: DRUG

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.

OM/HCTZ 40/12.5

Olmesartanmedoxomil (OM) /Hydrochlorothiazide (HCTZ)40/12.5 mg tablets.

Group Type: EXPERIMENTAL

OM/HCTZ 40/12.5

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Treatment; Treatment

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

INDUSTRY

Sponsor Role: collaborator

Menarini Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Fogari, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Clinic Policlinico San Matteo University of Pavia Italy

Locations

Rijeka, , Croatia

Slavonski Brod, , Croatia

Split, , Croatia

Varaždin, , Croatia

Zadar, , Croatia

Zagreb, , Croatia

Benátky nad Jizerou, , Czechia

Bílovec, , Czechia

Brodce, , Czechia

Jablonec nad Nisou, , Czechia

Mladá Boleslav, , Czechia

Prague, , Czechia

Rokycany, , Czechia

Tábor, , Czechia

Teplice, , Czechia

Uničov, , Czechia

Aalborg, , Denmark

Ballerup Municipality, , Denmark

Vejle, , Denmark

Berlin, , Germany

Cologne, , Germany

Dresden, , Germany

Einbeck, , Germany

Essen, , Germany

Giengen an der Brenz, , Germany

Großheirath, , Germany

Hamburg, , Germany

Hanau, , Germany

Heidelberg, , Germany

Künzing, , Germany

Leipzig, , Germany

Lollar, , Germany

Mannheim, , Germany

München, , Germany

Nuremberg, , Germany

Ashkelon, , Israel

Beersheba, , Israel

Haifa, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Nahariya, , Israel

Petah Tikva, , Israel

Tel Aviv, , Israel

Tel Litwinsky, , Israel

Busto Arsizio, , Italy

Ferrara, , Italy

Pavia, , Italy

Pisa, , Italy

San Daniele del Friuli, , Italy

Sassari, , Italy

Somma Lombardo, , Italy

Venezia, , Italy

Bialystok, , Poland

Gdansk, , Poland

Gdynia, , Poland

Lublin, , Poland

Płock, , Poland

Warsaw, , Poland

Wąbrzeżno, , Poland

Baia Mare, , Romania

Brăila, , Romania

Bucharest, , Romania

Cluj-Napoca, , Romania

Oradea, , Romania

Suceava, , Romania

Countries

Croatia; Czechia; Denmark; Germany; Israel; Italy; Poland; Romania

References

Fogari R, Taddei S, Holm-Bentzen M, Baszak J, Melani L, Schumacher K. Efficacy and safety of olmesartan medoxomil 40 mg/hydrochlorothiazide 12.5 mg combination therapy versus olmesartan medoxomil 40 mg monotherapy in patients with moderate to severe hypertension: a randomized, double-blind, parallel-group, multicentre, multinational, phase III study. Clin Drug Investig. 2010;30(9):581-97. doi: 10.2165/11536710-000000000-00000.

Reference Type: DERIVED

PMID: 20593911 (View on PubMed)

Other Identifiers

CS866CM-B-E303

Identifier Type: -

Identifier Source: org_study_id