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 Ingelheim31,546 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Purpose

PREVENTION

Enrollment

31,546

Conditions

Cardiovascular Diseases

Interventions

Eligibility

Sex: ALLMin age: 55 Years

Medical Language ↔ Plain English

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.

Locations (732)

502.373.0256 Boehringer Ingelheim Investigational Site

Athens, Alabama, United States

502.373.0251 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

502.373.0182 Boehringer Ingelheim Investigational Site

Phoenix, Arizona, United States

502.373.0188 Boehringer Ingelheim Investigational Site

Phoenix, Arizona, United States

502.373.0189 Boehringer Ingelheim Investigational Site

Tucson, Arizona, United States

Outcomes

Primary Outcomes

ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke and Hospitalization for Congestive Heart Failure

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of the following defined endpoints, Cardiovascular Death, Non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.

Time frame: 56 months

ONTARGET. 3-fold Composite Endpoint of Doubling of Serum Creatinine, Progression to End Stage Renal Disease (ESRD) and All-cause Mortality in Diabetic Nephropathy Patients

ESRD is defined by initiation of dialysis, need for renal transplantation, or eGFR \<15 mL/min/1.73 m². Diabetic nephropathy patients are diabetic patients with macro-albuminuria assessed as a Urinary Albumin Creatinine Ratio (UACR) ≥300 mg/g Crea at baseline. These renal outcomes were not adjudicated (apart from death).

Time frame: 56 months

TRANSCEND. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke and Hospitalization for Congestive Heart Failure

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND). Time to first event analysis of the following defined endpoints, Cardiovascular Death, Non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.

Time frame: 56 months

Secondary Outcomes

ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of the following defined endpoints, non-fatal myocardial infarction or non-fatal stroke

Time frame: 56 months

ONTARGET. Cardiovascular Death

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to the first event analysis of the endpoint cardiovascular death.

Time frame: 56 months

ONTARGET. Non-fatal Myocardial Infarction

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to the first event analysis of the endpoint non-fatal myocardial infarction.

Time frame: 56 months

ONTARGET. Non-fatal Stroke

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of the endpoint non-fatal stroke.

Time frame: 56 months

ONTARGET. Hospitalization for Congestive Heart Failure

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to the first event analysis of the endpoint hospitalization for congestive heart failure.

Time frame: 56 months

ONTARGET. Doubling of Serum Creatinine in Diabetic Nephropathy Patients

Diabetic nephropathy patients are diabetic patients with macro-albuminuria assessed as a Urinary Albumin Creatinine Ratio (UACR) ≥300 mg/g Crea at baseline.

Time frame: 56 months

ONTARGET. Progression to End Stage Renal Disease (ESRD) in Diabetic Nephropathy Patients

Time frame: 56 months

ONTARGET. All-cause Mortality in Diabetic Nephropathy Patients

Diabetic nephropathy patients are diabetic patients with macro-albuminuria assessed as a Urinary Albumin Creatinine Ratio (UACR) ≥300 mg/g Crea at baseline.

Time frame: 56 months

ONTARGET. Doubling of Serum Creatinine

ONTARGET. Nephropathy subcategory: doubling of serum creatinine

Time frame: 56 months

ONTARGET. Progression to ESRD

ONTARGET. Nephropathy subcategory: Progression to ESRD. Progression to ESRD is defined as initiation of dialysis, need for renal transplantation, or eGFR \<15 mL/min/1.73 m².

Time frame: 56 months

ONTARGET. New Microalbuminuria

ONTARGET. Nephropathy subcategory: New microalbuminuria. New microalbuminuria is defined as Urinary Albumin Creatinine Ratio ≥30 mg/g Crea in patients with a Urinary Albumin Creatinine Ratio \<30 mg/g Crea at baseline.

Time frame: 56 months

ONTARGET. New Macroalbuminuria

ONTARGET. Nephropathy subcategory: New macroalbuminuria. New macroalbuminuria is defined as Urinary Albumin Creatinine Ratio ≥300 mg/g Crea in patients with a Urinary Albumin Creatinine Ratio \<300 mg/g Crea at baseline.

Time frame: 56 months

ONTARGET. Combined Endpoint of Doubling of Serum Creatinine, Progression to ESRD, New Microalbuminuria, or New Macroalbuminuria

ONTARGET. Nephropathy subcategory: Combined endpoint of doubling of serum creatinine, progression to ESRD, new microalbuminuria, or new macroalbuminuria

Time frame: 56 months

ONTARGET. Normalisation From Micro- or Macroalbuminuria to Normoalbuminuria

ONTARGET. Nephropathy subcategory: Normalisation from micro- or macroalbuminuria to normoalbuminuria. Normalisation from micro- or macroalbuminuria to normoalbuminuria is defined as UACR \<30 mg/g Crea in patients with a UACR ≥30 mg/g Crea at baseline.

Time frame: 56 months

ONTARGET. Newly Diagnosed Congestive Heart Failure

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to the first event analysis of the endpoint Newly diagnosed Congestive Heart failure.

Time frame: 56 months

ONTARGET. Cardiovascular Revascularization Procedure

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET).

Time frame: 56 months

ONTARGET. Newly Diagnosed Diabetes

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to the first event analysis of the endpoint Newly diagnosed Diabetes. Only calculated for those patients without diabetes at baseline.

Time frame: 56 months

ONTARGET. Cognitive Decline

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of the endpoint cognitive decline i.e. Comparison of the Mini mental state Evaluation (MMSE) of patients at baseline with that at the 2years and end of trial. A decrease in MMSE from baseline represents a cognitive decline. This outcome measure is only available for those patients who had MMSE at baseline.

Time frame: 56 months

ONTARGET. New Onset of Atrial Fibrillation

The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of endpoint new onset of atrial fibrillation.

Time frame: 56 months

TRANSCEND. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND). Time to first event analysis of the following defined endpoints, Cardiovascular Death, Non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.

Time frame: 56 months

TRANSCEND. Cardiovascular Death

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND). Time to the first event analysis of the endpoint cardiovascular death.

Time frame: 56 months

TRANSCEND. Non-fatal Myocardial Infarction

Time frame: 56 months

TRANSCEND. Non-fatal Stroke

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

Time frame: 56 months

TRANSCEND. Hospitalization for Congestive Heart Failure

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

Time frame: 56 months

TRANSCEND. Doubling of Serum Creatinine

TRANSCEND. Nephropathy subcategory: doubling of serum creatinine

Time frame: 56 months

TRANSCEND. Progression to ESRD

TRANSCEND. Nephropathy subcategory: Progression to ESRD. Progression to ESRD is defined as initiation of dialysis, need for renal transplantation, or eGFR \<15 mL/min/1.73m²

Time frame: 56 months

TRANSCEND. New Microalbuminuria

TRANSCEND. Nephropathy subcategory: New microalbuminuria. New microalbuminuria is defined as UACR ≥30 mg/g creatinine \[Crea\] in patients with a UACR \<30 mg/g Crea at baseline

Time frame: 56 months

TRANSCEND. New Macroalbuminuria

TRANSCEND. Nephropathy subcategory: New macroalbuminuria. New macroalbuminuria is defined as UACR ≥300 mg/g creatinine \[Crea\] in patients with a UACR \<300 mg/g Crea at baseline

Time frame: 56 months

TRANSCEND. Combined Endpoint of Doubling Serum Creatinine, Progression to ESRD, New Microalbuminuria or New Macroalbuminuria

TRANSCEND. Nephropathy subcategory: Combined endpoint of doubling serum creatinine, progression to ESRD, new microalbuminuria or new macroalbuminuria

Time frame: 56 months

TRANSCEND. Normalisation From Micro- or Macroalbuminuria to Normoalbuminuria

TRANSCEND. Nephropathy subcategory: Normalisation from micro- or macroalbuminuria to normoalbuminuria. Normalisation from micro- or macroalbuminuria to normoalbuminuria is defined as UACR \<30 mg/g Crea in patients with a UACR ≥30 mg/g Crea at baseline.

Time frame: 56 months

TRANSCEND. New Onset of Atrial Fibrillation

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

Time frame: 56 months

TRANSCEND. Cognitive Decline

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND). Time to first event analysis of the endpoint cognitive decline i.e. Comparison of the Mini mental state Evaluation (MMSE) of patients at baseline with that at the 2years and end of trial. A decrease in MMSE from baseline represents a cognitive decline. This outcome measure is only available for those patients who had MMSE at baseline.

Time frame: 56 months

TRANSCEND. Newly Diagnosed Diabetes

Time frame: 56 months

TRANSCEND. Cardiovascular Revascularization Procedure

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

Time frame: 56 months

TRANSCEND. Newly Diagnosed Congestive Heart Failure

Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

Time frame: 56 months