Boehringer Ingelheim sets largest cardiovascular protection trial

MILAN, Italy — Boehringer Ingelheim has announced plans for the largest cardiovascular protection trial ever conducted on patients intolerant to angiotensin converting enzyme (ACE) inhibitors.

The study, announced at the European Society of Hypertension meeting, will examine the effects of the angiotensin III recepto antagonist (ARB) Micardis or telmisartan, on these patients. About 5,000 patients worldwide will be enrolled in the study.

The trial is called Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease or TRANSCEND. It will parallel the objectives of the ONTARGET cardiovascular protection trial, one of the largest, most ambitious clinical studies to investigate the role of an ARB in the prevention of stroke, myocardial infarction, hospitalization for congestive heart failure (CHF) and cardiovascular death in a combined endpoint.

Boehringer Ingelheim is the sole sponsor of both TRANSCEND and ONTARGET.

"TRANSCEND will be a significant complement to the ONTARGET trial, a study we anticipate will have a major impact on cardiovascular disease prevention," said Dr. Roland Schmieder of the University Erlangen Nurnberg.

"The goal of TRANSCEND and ONTARGET is to fully understand the potential of ARBs so that physicians can offer an effective and tolerable treatment regimen to the broadest range of patients," he added.

ONTARGET stands for Ongoing Telmisartan Alone and In Combination with Ramipril Global Endpoint Trial. It is expected to provide data on an ARB in a setting comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial in 1999.

The HOPE trial found that the ACE inhibitor ramipril reduces the combined risk of stroke, myocardial infarction and cardiovascular death by 22 percent. Boehringer Ingelheim announced the ONTARGET study in March.

"TRANSCEND is an important study that examines the effects of an ARB in a much neglected group – individuals who cannot tolerate an ACE inhibitor," said ONTARGET lead investigator Prof. Salim Yusuf of Hamilton, Canada.

"At present, many physicians extrapolate and assume that an ARB will be effective in this group. It will be very important to get hard evidence and TRANSCEND will provide this," he said.

Side-effects associated with ACE inhibitors include intolerable cough, renal dysfunction and orthostatic hypotension.

"These side-effects can result in discontinuation of the medication, therefore it is particularly important for ACE inhibitor-intolerant patients to have a safe and effective therapeutic option," said Schmieder.

TRANSCEND is a double-blind, parallel-group study that will begin this year and will be completed in approximately 5.5 years. It will run simultaneously with ONTARGET and will assess the ONTARGET study’s objectives for treatment with 80 mg Micardis versus placebo in patients who are intolerant to ACE inhibitors.

The primary objective of the study is the effect of Micardis on the composite endpoint of cardiovascular mortality, stroke, acute myocardial infarction and hospitalization for congestive heart future.

The secondary objective of TRANSCEND is its impact on the incidence of revascularization procedures, newly diagnosed diabetes, dementia, new onset atrial fibrillation and microvascular complications of diabetes.

Patients over 55 years old with a history of coronary artery disease, stroke, peripheral vascular disease or type I or II diabetes with end-organ damage may be eligible for enrollment. Heart failure patients are excluded from the study.

The study will assess the efficacy of the angiotensin II receptor blocker Micardis alone, and in combination with the ACE inhibitor ramipril, compared to the efficacy of ramipril alone.

The composite cardiovascular endpoint will be the reduction of the risk of cardiovascular mortality, stroke, myocardial infarction and hospitalization for CHF. This large international study of about 23,400 patients will be conducted in 39 countries.

The Boehringer Ingelheim group of companies, headquartered in Ingelheim, Germany, is one of the 20 leading pharmaceutical corporations in the world.

In 2000, it posted revenues of more than six billion euros. It has some 140 affiliate companies worldwide, and focuses on human pharmaceuticals and animal health.

The human pharmaceuticals business, which accounts for 95 percent of sales, is comprised of prescription medicines, consumer health care products and chemicals and biopharmaceuticals for industrial customers.

Research and development, production and distribution facilities are located around the world. In 2000, Boehringer Ingelheim spent almost one billion euros on R&D, equivalent to 16 percent of net sales.

For more information on Boehringer Ingelheim, visit www.boehringer-ingelheim.com. For more information on ONTARGET and TRANSCEND, visit www.ontarget-micardis.com.