Effectiveness and Safety of Ramipril Alone Compared With Telmisartan Alone and in Combination With Ramipril in Patients at High Risk for Cardiovascular Events. Patients Intolerant to Ramipril Were Entered in TRANSCEND, Telmisartan Compared to Placebo.

Boehringer Ingelheim

Status and phase: Completed; Phase 4

Conditions: Cardiovascular Diseases

Treatments: Drug: Ramipril; Drug: Telmisartan; Drug: Combination of Telmisartan and Ramipril

Study type: Interventional

Funder types: Industry

Identifiers

NCT00153101

502.373

Details and patient eligibility

About

The Ongoing Telmisartan Alone and in combination wiht Ramipril Global Endpoint trial (ONTARGET): The primary objectives are to determine if (a) telmisartan 80mg daily and ramipril 10mg daily combination therapy is more effective in reducing the composite endpoint of Cardiovascular Death (CV) death, Myocardial infarction (MI), stroke or hospitalization for Congestive Heart Failure (CHF) compared with ramipril 10mg alone; and (b) telmisartan 80mg daily is at least as effective as (i.e. not less effective than) ramipril 10mg daily, on this endpoint.

Telmisartan Randomised Assessment Study in Angiotension converting Enzyme inhibitor intolerant subjects with Cardiovascular Disease. (TRANSCEND): The primary objective of the study is to determine if treatment with telmisartan 80mg daily is superior to placebo reducing the composite endpoint of Cardiovascular Death (CV), Myocardial Infarction ( MI)I, stroke or hospitalization for Congestive Heart Failure (CHF) in patients who are intolerant to Angiotension Converting Enzyme inhibitors.

Enrollment: 31,546 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Coronary Artery Disease: Previous Myocardial infarction(> 2 days prior to informed consent), or stable or previous unstable angina (> 30 days prior to informed consent) with documented multivessel coronary artery disease or a positive stress test, or multivessel Percutaneous Transluminal Coronary Angioplasty (> 30 days prior to informed consent), or previous multivessel Coronary Artery Bypass Grafting without angina (if surgery performed > 4 years prior to informed consent) or with recurrent angina after surgery.

Other High Risk:

1. Peripheral Arterial Disease: Previous limb bypass surgery or angioplasty or amputation, intermittent claudication on history with ankle/arm Blood Pressure ratio < 0.8 on at least one side, or significant stenosis by angiography or non-invasive testing
2. Previous stroke
3. Transient ischemic Attack > 7 days and < 1 year prior to informed consent
4. Diabetes Mellitus (types I or II): with evidence of end-organ damage (retinopathy, Left ventricular hypertrophy, micro or macro albuminuria), or any evidence of previous cardiac or vascular disease.

No definite and specific indication or contraindication for any of the study treatments. Written informed consent.

Exclusion criteria

A. Medication use:

1. Inability to discontinue Angiotension Converting Enzyme (ACE) inhibitors or Angiotension 2 receptor antagonists (AIIAs).
2. Patients with known hypersensitivity or intolerance to Angiotension 2 receptor antagonists (AIIAs) or Angiotension Converting Enzyme (ACE)inhibitors.

NOTE: Patients with known intolerance to Angiotension Converting Enzyme inhibitor intolerance ( ACE-I) can be enrolled in the TRANSCEND study.

B. Cardiovascular disease:

1. Symptomatic congestive heart failure.
2. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).
3. Constrictive pericarditis.
4. Complex congenital heart disease.
5. Syncopal episodes of unknown etiology < 3 months before informed consent.
6. Planned cardiac surgery or angioplasty within three months.
7. Uncontrolled hypertension on treatment (i.e.Blood pressure ( BP) > 160/100).
8. Heart transplant recipient.
9. Strokes due to subarachnoid hemorrhage

C. Other conditions:

1. Significant renal disease defined as:

   1. Renal artery stenosis;
   2. Creatinine clearance < 0.6 ml/min or serum creatinine > 265 umol/L (> 3.0 mg/dL);
   3. Hyperkalemia: potassium > 5.5 mmol/L.
   4. Proteinuria* (for TRANSCEND only).

2. Hepatic dysfunction as defined by the following laboratory parameters: Serum Glutamate Pyruvate Transaminase( SGPT) Alaninaminotransferase (ALT) or Serum Glutamic Oxaloacetic Transaminase (SGOT) Aspartate aminotransferase (AST) > than 4 times upper limit of normal or additional criteria for hepatic impairment the upper limit of normal range, total Bilirubin > 20 umol/L, biliary obstructive disorders.

3. Uncorrected volume depletion or sodium depletion.

4. Primary aldosteronism.

5. Hereditary fructose intolerance.

6. Any other major non-cardiac illness expected to reduce life expectancy or interfere with study participation.

7. Patient is simultaneously taking another experimental drug.

8. Patient with significant disability that precludes regular attendance at clinic for follow-up.

9. Patient has sufficient disability or other incapacity that precludes regular attendance at clinic for follow-up.

10. Unable or unwilling to provide written informed consent.