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.

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00153101
First received: September 9, 2005
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Cardiovascular Diseases
Drug: Telmisartan
Drug: Combination of Telmisartan and Ramipril
Drug: Ramipril
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Prevention
Official Title: ONTARGET ONgoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial A Large, Simple Randomized Trial of an Angiotensin II Receptor Antagonist (Telmisartan) and an ACE-Inhibitor (Ramipril) in Patients at High Risk for Cardiovascular Events and TRANSCEND Telmisartan Randomized AssessmeNt Study in aCE iNtolerant Subjects With Cardiovascular Disease. A Parallel Study Comparing the Effects of Telmisartan With Placebo and Outcomes in Patients at High Risk for Cardiovascular Events and Intolerant to ACE-I.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke and Hospitalization for Congestive Heart Failure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 56 months ] [ Designated as safety issue: No ]

    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).


  • TRANSCEND. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke and Hospitalization for Congestive Heart Failure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • ONTARGET. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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

  • ONTARGET. Cardiovascular Death [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to the first event analysis of the endpoint cardiovascular death.

  • ONTARGET. Non-fatal Myocardial Infarction [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. Non-fatal Stroke [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of the endpoint non-fatal stroke.

  • ONTARGET. Hospitalization for Congestive Heart Failure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. Doubling of Serum Creatinine in Diabetic Nephropathy Patients [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Diabetic nephropathy patients are diabetic patients with macro-albuminuria assessed as a Urinary Albumin Creatinine Ratio (UACR) ≥300 mg/g Crea at baseline.

  • ONTARGET. Progression to End Stage Renal Disease (ESRD) in Diabetic Nephropathy Patients [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. All-cause Mortality in Diabetic Nephropathy Patients [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Diabetic nephropathy patients are diabetic patients with macro-albuminuria assessed as a Urinary Albumin Creatinine Ratio (UACR) ≥300 mg/g Crea at baseline.

  • ONTARGET. Doubling of Serum Creatinine [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    ONTARGET. Nephropathy subcategory: doubling of serum creatinine

  • ONTARGET. Progression to ESRD [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. New Microalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. New Macroalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. Combined Endpoint of Doubling of Serum Creatinine, Progression to ESRD, New Microalbuminuria, or New Macroalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    ONTARGET. Nephropathy subcategory: Combined endpoint of doubling of serum creatinine, progression to ESRD, new microalbuminuria, or new macroalbuminuria

  • ONTARGET. Normalisation From Micro- or Macroalbuminuria to Normoalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. Newly Diagnosed Congestive Heart Failure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. Cardiovascular Revascularization Procedure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET).

  • ONTARGET. Newly Diagnosed Diabetes [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. Cognitive Decline [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • ONTARGET. New Onset of Atrial Fibrillation [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    The Ongoing Telmisartan Alone and combination with Ramipril global Endpoint trial (ONTARGET). Time to first event analysis of endpoint new onset of atrial fibrillation.

  • TRANSCEND. Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • TRANSCEND. Cardiovascular Death [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • TRANSCEND. Non-fatal Myocardial Infarction [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND). Time to the first event analysis of the endpoint non-fatal myocardial infarction.

  • TRANSCEND. Non-fatal Stroke [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

  • TRANSCEND. Hospitalization for Congestive Heart Failure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

  • TRANSCEND. Doubling of Serum Creatinine [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    TRANSCEND. Nephropathy subcategory: doubling of serum creatinine

  • TRANSCEND. Progression to ESRD [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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

  • TRANSCEND. New Microalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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

  • TRANSCEND. New Macroalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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

  • TRANSCEND. Combined Endpoint of Doubling Serum Creatinine, Progression to ESRD, New Microalbuminuria or New Macroalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    TRANSCEND. Nephropathy subcategory: Combined endpoint of doubling serum creatinine, progression to ESRD, new microalbuminuria or new macroalbuminuria

  • TRANSCEND. Normalisation From Micro- or Macroalbuminuria to Normoalbuminuria [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • TRANSCEND. New Onset of Atrial Fibrillation [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

  • TRANSCEND. Cognitive Decline [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    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.

  • TRANSCEND. Newly Diagnosed Diabetes [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND). Time to the first event analysis of the endpoint Newly diagnosed Diabetes. Only calculated for those patients without diabetes at baseline.

  • TRANSCEND. Cardiovascular Revascularization Procedure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).

  • TRANSCEND. Newly Diagnosed Congestive Heart Failure [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Telmisartan Randomized Assessment Study in Angiotension Converting Enzyme inhibitor intolerant subjects with cardiovascular disease (TRANSCEND).


Enrollment: 31546
Study Start Date: November 2001
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153101

  Show 732 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00153101     History of Changes
Obsolete Identifiers: NCT00034931
Other Study ID Numbers: 502.373
Study First Received: September 9, 2005
Results First Received: June 15, 2009
Last Updated: May 13, 2014
Health Authority: Argentina: National Administration of Medicines, Food and Medical Technology
Australia: Responsilble Ethics Committee
Austria: Ministry for Social Security and Generations
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control (SUKL)
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: AFFSAPS
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Greece: HELLENIC REPUBLIC MINISTRY OF HEALTH AND WELFARE NATIONAL ORGANISATION OF MEDICINES (EOF)
Hong Kong: Dept. of Health, Hong Kong
Hungary: National Institute of Pharmacy (OGYI), H-1051 Budapest
Ireland: The Irish Medicines Board
Italy: Comitato Etico delle Aziende Sanitarie della Regione Umbria
Korea, Republic of: Korea Food and Drug Administration (KFDA)
Malaysia: Drug Control Authority
Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Multicentre Ethics Committee/Medsafe
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Philippines: Bureau of Pharmaceutical Affairs, Department of Health
Poland: CEBK, Warsaw
Portugal: INFARMED, National Authority of Medicines and Health Products, IP
Russia: Ministry of Health of the Russian Federation
Singapore: Centre of Drug Administration
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
South Africa: Medicines Control Council
Spain: Ministry of Health
Sweden: Medical Product Agency
Switzerland: Swissmedic Schweizerisches Heilmittelinstitut (Swiss Agency for Therapeutic Products)
Taiwan: Dept. of Health, Executive Yuan, Taiwan
Thailand: Bureau of Pharmaceutical Affairs, Department of Health
Turkey: Ministry of Health Central Ethics Committee
Ukraine: State Pharmacology Centre of the Ministry of Health of Ukraine
United Arab. Emirates: Medical Affairs Department of Health and Medical Services, General Authority Health Services, Ministry of Health for Northern Emirates
United States: Food and Drug Administration

Additional relevant MeSH terms:
Cardiovascular Diseases
Ramipril
Telmisartan
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers

ClinicalTrials.gov processed this record on August 28, 2014