Effect of Pioglitazone compared to a combination therapy with Ramipril and to a Ramipril monotherapy on low grade inflammation and vascular function in patients with increased cardiovascular risk and an activated inflammationA randomized double-blinded phase II study

• Conditions: on-diabetic hypertensive patients with a hsCRP value > 1.0 mg/L < 10.0 mg/L and pretreated with ACE inhibitors for at least 12 weeks are eligible for study participation.; MedDRA version: 8.1Level: LLTClassification code 10003601Term: Atherosclerosis

• Registration Number: EUCTR2006-004028-35-DE
• Lead Sponsor: Takeda Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-11-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

1.Age 30-75 years
2.Arterial hypertension
3.Stable treatment with an ACE inhibitor at least for 12 weeks
4.High sensitive CRP value > 1.0 mg/L < 10.0 mg/L

written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Manifest or newly detected diabetes mellitus type 2 according to WHO criteria
2.Type 1 diabetes
3.Acute infections
4.Chronic inflammatory diseases which cause elevated CRP-values (e.g. rheumatic diseases, pyelonephritis, osteomyelitis)
5.Use of acetyl salicylic acid and/or NSAIDs 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
6.Uncontrolled hypertension (repeated blood pressure > 180/100 mmHg for at least three times within two weeks); persistent hypotension (systolic < 90 mmHg) or haemodynamic instability
7.Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
8.History of severe or multiple allergies
9.Treatment with any other investigational drug within 3 months before trial entry
10.Progressive fatal disease
11.History of drug or alcohol abuse within the last 5 years
12.A history of significant cardiovascular (NYHA stage I – IV, haemodynamic relevant aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy), respiratory, gastrointestinal, hepatic (ALAT > 2.5 times the normal reference range), renal (creatinine > 2.0 mg/dL), or haematological disease, history of macular oedema
13.State after kidney transplantation, haemodynamic relevant renal artery stenosis (bilateral or unilateral in case of single kidney)
14.Blood donation within the last 30 days
15.Serum potassium > 5.5 mmol/L
16.History of hyperaldosteroism
17.Pregnancy or breast feeding
18.Sexually active women of childbearing potential not consistently and correctly practicing highly effective birth control with a low failure rate (less than 1%) such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner.
19.Lack of compliance or other similar reason, that precludes satisfactory participation in the study according to investigators’ opinion
20.Treatment with thiazolidinediones within 3 months prior to screening
21.Acute myocardial infarction, open heart surgery or cerebral events (stroke / TIA) within 30 days prior to screening visit
22.Patient is an employee or at least dependence of an investigator and/or the sponsor or of an institution directly involved in the study or other trials under the investigator’s direction
23.If statin therapy applicable: Change of medication within the last 12 weeks
24. History of angioneurotic oedema (hereditary or idiopatic as consequence of previous ACE-inhibitor treatment)
25. Dialysis or hemofiltration
26. LDL apheresis with dextran sulfate
27. Sensitation with toxic agents derived from insects

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effect of Pioglitazone compared to a combination therapy with Ramipril and to Ramipril alone on low grade inflammation and vascular function in patients with increased cardiovascular risk and an activated inflammation. The primary efficacy variable of the study is the change of hsCRP value after 12 weeks of treatment as compared to baseline.;Secondary Objective: To investigate the effect of pioglitazone compared to a combination therapy with ramipril and to a ramipril monotherapy on several laboratory parameters such as lipids, inflammatory markers, parameter of vascular function and other parameter of special interest.;Primary end point(s): The primary efficacy variable of the study is the change of hsCRP value after 12 weeks of treatment as compared to baseline