Clinical trial NCT00296218: ARCHIPELAGO: Irbesartan in Patients With Acute Coronary Syndrome Without ST Segment Elevation
Official title: Randomized Comparison of a Two-month Regimen of Irbesartan Versus Enalapril on Cardiovascular Markers in Patients With Acute Coronary Syndrome Without ST Segment Elevation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Ischemia
Hypertension
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2006-02-24
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Primary Objective

* The main objective of this study is to assess if a two-month regimen of irbesartan in patients hospitalized for acute coronary syndrome without ST segment elevation can reduce inflammation markers (ie hsCRP), in comparison to a similar regimen of enalapril.

Secondary Objectives

* To compare both regimens on several other biological parameters which have demonstrated their relevance and their predictive clinical value (ie BNP, microalbuminuria, troponin I ...) in this patient population.
* To compare on the above parameters the early initiation of treatment versus the initiation of treatment at hospital discharge.


Eligibility criteria: The following information on clinical trials is provided for information purposes only to allow patients and physicians to have an initial discussion about the trial. This information is not intended to be complete information about the trial, to contain all considerations that may be relevant to potential participation in the trial, or to replace the advice of a personal physician or health professional.

Main criteria are listed hereafter:

Inclusion Criteria

* Patient hospitalised with ischemic symptoms (last episode within the last 48 hours before randomization) and at least one of the following characteristics of NSTEACS (non-ST-segment-elevation acute coronary syndromes):

  * ECG ST or T changes (ST depression or transient elevation of at least 1mm or T wave changes in at least 2 leads)
  * Positive troponin (according to local threshold)

Exclusion Criteria

* Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study WOCBP using a prohibited contraceptive method (not applicable)
* Women who are pregnant or breast feeding
* Women with a positive pregnancy test on enrolment or prior to study drug administration
* Patient with dementia
* Persistent ST segment elevation at ECG
* Systolic blood pressure \< 100 mmHg
* Bilateral stenosis of renal artery
* Creatinine clearance \< or = 30ml/mn
* Congestive heart failure with symptoms consistent with New York Heart Association (NYHA) class III or IV.
* Aortic or mitral valve stenosis
* Hypertrophic cardiomyopathy
* Connective tissue disease with vascular involvement
* Angioplasty, surgery or trauma within the last 3 months
* Coronarography or angioplasty planned to be performed or performed before baseline sampling
* Febrile (≥ 38°C) disease, known concomitant viral or bacterial infection, chronic auto immune disease, chronic inflammatory disease, known cancer in evolution
* Hyperkalemia: serum potassium \> 5.5mmol/l
* Sensitivity or intolerance to Angiotensin receptor blockers (ARBs) : olmesartan, candesartan, irbesartan, eprosartan, losartan, telmisartan, valsartan and/or any other ARB currently or previously in development.
* Sensitivity or intolerance to Angiotensin-converting Enzyme Inhibitors (ACE-I) : benazepril, captopril, enalapril, lisinopril, trandolapril, ramipril, quinapril, and/or any other ACE-I currently or previously in development.
* Chronic steroid or non-steroidal anti inflammatory drugs (NSAIDs) use. Aspirin is permitted.
* Treatment with allopurinol or procaïnamide
* Concomitant use of potassium sparing diuretics (eg. spironolactone, triamterene or amiloride), potassium preparations or salt substitutes containing potassium
* Treatment with Lithium
* Immunosupressive medication
* Administration of any other investigational drug in the last 30 days before enrolment and during the course of the study
* Treatment with ARB or ACE inhibitor within the last 3 days.

Primary outcomes:
measure: comparison of the relative change from baseline in hsCRP at day 60 between the two treatment groups
Secondary outcomes:
measure: Relative change from baseline of hsCRP at discharge
measure: Changes from baseline in BNP and Microalbuminuria (MAU) at discharge and day 60
measure: Change of Troponin I from baseline at discharge
measure: In addition at baseline, discharge and D60 the following parameters will be evaluated and their evolution compared in the two treatment groups: IL6, CD 40 L, sPLA2 and Lp-PLA2, IMA, MMP-9, MPO (myeloperoxydase), aldosterone
measure: Blood pressure at discharge, D15 and D60.
measure: The early versus late (at hospital discharge) initiation of treatment will also be evaluated on the above-listed parameters.
measure: & Safety outcomes
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis
state: New Jersey
city: Brussels
country: Belgium
facility: Sanofi-Aventis
city: Laval
country: Canada
facility: Sanofi-Aventis
city: Paris
country: France
facility: Sanofi-Aventis
city: Berlin
country: Germany
facility: Sanofi-Aventis
city: Budapest
country: Hungary
facility: Sanofi-Aventis
city: Milan
country: Italy
facility: Sanofi-Aventis
city: Gouda
country: Netherlands
facility: Sanofi-Aventis
city: Barcelona
country: Spain
facility: Sanofi-Aventis
city: Meyrin
country: Switzerland
facility: Sanofi-Aventis
city: Guildford
country: United Kingdom
facility: Sanofi-Aventis
Study officials:
affiliation: Sanofi
name: Catherine Domenger, MD
role: STUDY_DIRECTOR
References:
citation: Montalescot G, Drexler H, Gallo R, Pearson T, Thoenes M, Bhatt DL. Effect of irbesartan and enalapril in non-ST elevation acute coronary syndrome: results of the randomized, double-blind ARCHIPELAGO study. Eur Heart J. 2009 Nov;30(22):2733-41. doi: 10.1093/eurheartj/ehp301. Epub 2009 Aug 21.