Ramipril in Rheumatoid Arthritis

Condition(s) targeted: Arthritis, Rheumatoid

Intervention: Ramipril (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
Ali Shokry, Study Director, Affiliation: Sanofi-Aventis

The present study is designed to evaluate the hypothesis that the Angiotensin‐Converting Enzyme (ACE) inhibitor Ramipril improves vascular function and reduces markers of low-grade chronic inflammation and oxidative stress in patients with Rheumatoid Arthritis.

Official title: Effects of Ramipril on Endothelial Function in Patients With Rheumatoid Arthritis

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome: Endothelial dysfunction evaluated on weeks 8 and 16.

Secondary outcome: Alteration of inflammatory parameters: C-reactive Protein, TNFa, Interleukin 6 on weeks 8 and 16.

Detailed description: The effect of an 8-week treatment with either ramipril or placebo is studied using a randomized, double-blind, and crossover protocol. After given written informed consent, baseline characteristics including physical examination, ECG, blood sample and a noninvasive assessment of endothelial function are obtained. The patients are randomly assigned to receive either ramipril 10mg (up-titration-scheme: starting with 2. 5mg in Week1, then 5mg in Week2 followed by 2-5mg for the final 6 weeks) followed by placebo or vice versa. The individual disease-modifying antirheumatic drug therapy is continued throughout the study. The examinations are repeated after 8 weeks treatment of the first and 8 weeks after the second study drug. At week 1 and 2 in each treatment period a safety visit is scheduled.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- patients with rheumatoid arthritis (4 out of 7 ARA criteria must be fulfilled to

establish diagnosis) on stable background therapy for the last three months

- endothelial dysfunction (FMD < 4%, FMD: Flow-Mediated-Dilatation)

- non-smokers

Exclusion Criteria:

- previous myocardial infarction, coronary intervention or coronary surgery

- previous treatment with statins in the last 6 months

- previous treatment with ACE-inhibitors in the last 6 months

- uncontrolled hypertension SAP/DAP > 160/90 mmHg (SAP: Systolic Arterial Pressure,

DAP: Diastolic Arterial Pressure)

- dyslipidemia (LDL-cholesterol > 4. 9 mmol)

- normal CRP < 3 mg/l

- overweight BMI > 35kg/m2

- anaemia (hemoglobin < 10g/dl)

- kidney disease (creatinine > 150 umol/l)

- insulin-dependent diabetes mellitus

- congestive heart failure (> NYHA I)

- AV-Block>I

- pregnancy

- angio-edema

- malignancy or chronic infection

- drug abuse

Starting date: June 2004
Ending date: July 2006
Last updated: November 23, 2007