Efficacy Study of Pioglitazone and Ramipril Combination Therapy in Treating Non-diabetic Hypertensive Patients.

NCT ID: NCT00770497

Last Updated: 2010-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 172 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2008-05-31

Brief Summary

The purpose of this study is to determine the effects of pioglitazone, once daily (QD), on low grade inflammation and vascular function in hypertensive patients.

Detailed Description

Patients with insulin resistance and an activated inflammation are prone for cardiovascular complications like myocardial infarction or stroke. Pharmacological interventions reducing vascular inflammation are thought to reduce cardiovascular risk in diabetic and in non-diabetic patients.

Intervention with ACE inhibitors like ramipril is an established and widely used treatment for patients with high blood pressure, proven to reduce cardiovascular risk. Treatment of non-diabetic patients with pioglitazone has shown to improve the cardiovascular risk profile in non-diabetic patients beyond its effect on blood glucose levels.

The purpose of this study is to evaluate effects on low grade inflammation and vascular function of pioglitazone in non-diabetic, hypertensive patients with pre treatment with angiotensin converting enzyme inhibitors (that will be replaced by the study medication at time of randomization).

Conditions

Inflammation; Hypertension

Study Design

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

Study Groups

Pioglitazone 15 mg to 30 mg QD

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

Pioglitazone 15 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for two weeks; increased to:

Pioglitazone 30 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for up to 10 weeks.

Pioglitazone 15 mg to 30 mg QD + Ramipril 2.5 mg to 5 mg QD

Group Type: ACTIVE_COMPARATOR

Pioglitazone and ramipril

Intervention Type: DRUG

Pioglitazone 15 mg, tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to:

Pioglitazone 30 mg, tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.

Ramipril 2.5 mg to 5 mg QD

Group Type: ACTIVE_COMPARATOR

Ramipril

Intervention Type: DRUG

Pioglitazone placebo-matching tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to:

Pioglitazone placebo-matching tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.

Interventions

Pioglitazone

Pioglitazone 15 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for two weeks; increased to:

Pioglitazone 30 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for up to 10 weeks.

Intervention Type: DRUG

Pioglitazone and ramipril

Pioglitazone 15 mg, tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to:

Pioglitazone 30 mg, tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.

Intervention Type: DRUG

Ramipril

Pioglitazone placebo-matching tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to:

Pioglitazone placebo-matching tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.

Intervention Type: DRUG

Other Intervention Names

ACTOS®; AD4833; ACTOS®; AD4833

Eligibility Criteria

Inclusion Criteria

• Has arterial hypertension.
• Is on stable treatment with an Angiotensin Converting Enzyme inhibitor at least for 12 weeks.
• Has a high sensitive C-Reactive Protein value greater than 1.0 mg/L and less than 10.0 mg/L.
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria

• Manifests or has newly detected diabetes mellitus type 2 according to World Health Organization criteria.
• Has Type 1 Diabetes.
• Has acute infections.
• Chronic inflammatory diseases which cause elevated CRP-values (e.g. rheumatic diseases, pyelonephritis or osteomyelitis).
• Use of acetyl salicylic acid and/or Non-steroidal Anti-inflammatory Drugs or Cox-2-inhibitors within the last 4 weeks prior to screening visit, use of Rifampicin within the last 12 weeks prior to screening visit.
• Uncontrolled hypertension (repeated blood pressure greater than 180/100 mmHg for at least three times within two weeks); persistent hypotension (systolic less than 90 mmHg) or hemodynamic instability.
• Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
• History of severe or multiple allergies.
• Treatment with any other investigational drug within 3 months before trial entry.
• Has a progressive, fatal disease.
• History of drug or alcohol abuse within the last 5 years.
• A history of significant cardiovascular (New York Heart Association stage I - IV, hemodynamic relevant aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy), respiratory, gastrointestinal, hepatic (alanine aminotransferase greater than 2.5 times the normal reference range), renal (creatinine greater than 2.0 mg/dL), or hematological disease, history of macular edema.
• State after kidney transplantation, hemodynamic relevant renal artery stenosis (bilateral or unilateral in case of single kidney).
• Blood donation within the last 30 days.
• Serum potassium greater than 5.5 mmol/L.
• History of hyperaldosteronism.
• Treatment with thiazolidinediones within 3 months prior to screening.
• Acute myocardial infarction, open heart surgery or cerebral events (stroke/transient ischemic attack) within 30 days prior to screening visit.
• If statin therapy applicable: Change of medication within the last 12 weeks.
• History of angioneurotic edema (hereditary or idiopathic as consequence of previous Angiotensin Converting Enzyme inhibitor treatment).
• Dialysis or hemofiltration.
• Low Density Lipoprotein apheresis with dextran sulphate.
• Allergic to toxic agents derived from insects.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Takeda Pharma GmbH, Aachen (Germany)

Principal Investigators

Medical Adviser Clinical Research

Role: STUDY_DIRECTOR

Takeda Pharma Gmbh, Aachen (Germany)

Locations

Deggingen, Baden-Wurttemberg, Germany

Rottweil, Baden-Wurttemberg, Germany

Spaichingen, Baden-Wurttemberg, Germany

Weilersbach, Bavaria, Germany

Hanover, Lower Saxony, Germany

Cologne, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Werne, North Rhine-Westphalia, Germany

Mainz, Rhineland-Palatinate, Germany

Schauenburg, Rhineland-Palatinate, Germany

Dresden, Saxony, Germany

Berlin, State of Berlin, Germany

Blankenhain, Thuringia, Germany

Countries

Germany

Related Links

http://general.takedapharm.com/content/file/pi.pdf?applicationcode=ab2d7112-8eb3-465a-8fda-35018a9eafb0&fileTypeCode=ACTOSPI

ACTOS® Package Insert

Other Identifiers

2006-004028-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-PIO-110

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1115-9194

Identifier Type: REGISTRY

Identifier Source: secondary_id

ATS K023

Identifier Type: -

Identifier Source: org_study_id

NCT00975624

Identifier Type: -

Identifier Source: nct_alias