Stroke Trials Registry

ONTARGET
ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial

Principal Investigator
Peter Sleight

PI Address
Oxford University
Oxford OX1 2JD, UK

Contact Address
Ingrid Copland
ONTARGET/TRANSCEND Research Coordinator
Population Health Research Institute
Hamilton General Hospital
McMaster Clinic, Rm 355
237 Barton St. East
Hamilton, ON L8L 2X2, Canada
Tel: 905-527-4322 ext. 44520

Email: Ingrid@ccc.mcmaster.ca

Contact Email
yusufs@mcmaster.ca

Sponsor

Trial Phase:	Phase IV
Study Size Actual:	25620
Study Size Planned:	31546
Centers Actual:	732
Centers Planned:	793
Min Age:	55
Follow-up Duration:	5 Years
ISRCTN#	NCT00153101

Status:
Completed as of September, 2009.

Purpose:
To determine if (a) telmisartan 80mg daily and ramipril 10mg daily combination therapy is more effective in reducing the composite endpoint of CV death, MI, stroke or hospitalization for 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.

Interventions:

Ramipril
Ramipril is used alone or in combination with other medications to treat high blood pressure. It is also used to reduce the risk of heart attack and stroke in patients at risk for these problems and to improve survival in patients with heart failure after a heart attack. Ramipril is in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten the blood vessels, so blood flows more smoothly and the heart can pump blood more efficiently.

Telmisartan
Telmisartan is used alone or in combination with other medications to treat high blood pressure. Telmisartan is in a class of medications called angiotensin II receptor antagonists. It works by blocking the action of certain chemicals that tighten the blood vessels, so blood flows more smoothly.

Location(s):
Asia, Australia, Europe, New Zealand, North and South America, Africa

Year Started: 2001

Year Finished: 2008

Year Published: 2009

Design:
Interventional, Prevention, Randomized, Double-Blind, Active Control, Parallel Assignment.

Inclusion Criteria
Coronary Artery Disease: Previous MI (> 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 PTCA (> 30 days prior to informed consent), or previous multivessel CABG without angina (if surgery performed > 4 years prior to informed consent) or with recurrent angina after surgery; other high risk: peripheral arterial disease: previous limb bypass surgery or angioplasty or amputation, intermittent claudication on history with ankle/arm BP ratio < 0.8 on at least one side, or significant stenosis by angiography or non-invasive testing; previous stroke; TIA > 7 days and < 1 year prior to informed consent; Diabetes Mellitus (types I or II): with evidence of end-organ damage (retinopathy, LVH, 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.

Exclusion Criteria
A. Medication use: inability to discontinue ACE-inhibitors or AIIA; known hypersensitivity or intolerance to AIIA?s or ACE-inhibitors;
B. Cardiovascular disease: symptomatic congestive heart failure; hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve);constrictive pericarditis; complex congenital heart disease; scyncopal episodes of unknown etiology < 3 months before informed consent; planned cardiac surgery or angioplasty within three months; uncontrolled hypertension on treatment (i.e. BP > 160/100); heart transplant recipient; strokes due to subarachnoid hemorrhage
C. Other conditions: significant renal disease defined as:
Renal artery stenosis; Creatinine clearance < 0.6 ml/min or serum creatinine > 265 ?mol/L (> 3.0 mg/dL); hyperkalemia: potassium > 5.5 mmol/L.; hepatic dysfunction as defined by the following laboratory parameters: SGPT (ALT) or SGOT (AST) > than 4 times upper limit of normal or additional criteria for hepatic impairment the upper limit of normal range, total Bilirubin > 20 ?mol/L, biliary obstructive disorders; uncorrected volume depletion or sodium depletion;
primary aldosteronism; hereditary fructose intolerance;
any other major non-cardiac illness expected to reduce life expectancy or interfere with study participation; patient is simultaneously taking another experimental drug; patient with significant disability that precludes regular attendance at clinic for follow-up; patient has sufficient disability or other incapacity that precludes regular attendance at clinic for follow-up; unable or unwilling to provide written informed consent.

Patient Involvement:
Eligible patients will be randomized to receive either ramipril, telmisartin, or a combination of the two. Patients will be followed for 4-6 years.

Primary Outcome:
Combined incidence of cardiovascular death, stroke, acute myocardial infarction (MI), and hospitalization for CHF (congestive heart failure).

Secondary Outcome:
Newly diagnosed CHF, revascularisation procedures, newly diagnosed diabetes, cognitive decline/dementia, nephropathy, unstable/worsening angina, transient ischemic attack, no-CV death.

Results:
Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). In conclusion, Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit.

Source of Information:
ONTARGET web site, Boehringer Ingelheim. Presented at 12th European Stroke Conference (May 2003). Presented at the 29th International Stroke Conference (February 2004).
Presented at the 2008 European Stroke Conference (May 2008).

Web Links and Publications:

Outcome Study ONTARGET.
ClinicalTrials.gov

Current ONTARGET Publication List

Effect of telmisartan on renal outcomes: a randomized trial.
Ann Intern Med 2009 Jul 7;151(1):1-10, W1-2

Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study.
J Hypertens 2009 Jul;27(7):1360-9

Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.
Lancet 2008 Aug 16;372(9638):547-53

Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial.
Lancet 2008 Sep 27;372(9644):1174-83

Cardiac and vascular protection: the potential of ONTARGET.
Medscape J Med 2008 Mar 26;10 Suppl:S7

Telmisartan, ramipril, or both in patients at high risk for vascular events.
N Engl J Med 2008 Apr 10;358(15):1547-59

The ONTARGET Trial Programme
Presented at the 29th International Stroke Conference (February 2004)

Telmisartan Fails to Protect Poststroke Patients Against Second Event When Compared to Placebo: Presented at ESC
http://www.docguide.com/news/content.nsf/NewsPrint/852571020057CCF68525744F006814DC

This information last updated on: 9/29/2009

Reviewed on: 09/28/2009.

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