INVEST: INternational VErapamil SR Trandolapril STudy

Condition(s) targeted: Hypertension; Coronary Artery Disease

Intervention: Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ) (Drug); Atenolol/HCTZ/Trandolapril (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Florida

Official(s) and/or principal investigator(s):
Carl J Pepine, MD, Principal Investigator, Affiliation: University of Florida

Because blood pressure affects the heart, blood vessels, kidneys, and the entire body, it is important to keep it as normal as possible. There are several different ways to control blood pressure and to prevent or limit the development of heart disease due to high blood pressure. The purpose of this study is to compare two treatments to see how well they work and the difference in their side effects. One treatment includes the use of a calcium antagonist drug (Isoptin sustained release [SR] or Verapamil SR). The other treatment excludes the calcium antagonist and may include a non-calcium antagonist drug called a beta blocker (Tenormin or Atenolol). Both treatments may also include medication called angiotensin converting enzyme (ACE) inhibitors and water pills. None of the drugs in this study are experimental, they are all approved by the Food and Drug Administration (FDA).

Official title: INternational VErapamil SR Trandolapril STudy

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: First occurrence of death or nonfatal myocardial infarction (MI) or nonfatal stroke

Secondary outcome:

Death

Nonfatal MI

Nonfatal stroke

Newly diagnosed diabetes

BP control

Cancer

Gastrointestinal (GI) bleeding

Alzheimer's Disease

Parkinson's Disease

Cardiovascular (CV) hospitalizations

Quality of life

Compliance

Detailed description: INVEST is an investigator initiated international, prospective, randomized study comparing two pharmacotherapy strategies to control hypertension in ambulatory patients with coronary artery disease (CAD). One strategy, the calcium antagonist care strategy, centers on a calcium antagonist (verapamil SR) followed by addition of an ACE inhibitor (trandolapril) and then diuretic (hydrochlorothiazide) as needed to achieve target blood pressures (BP). The other strategy, the non-calcium antagonist care strategy, uses a beta-blocker (atenolol) followed by addition of low-dose diuretic and then an ACE inhibitor (trandolapril) as needed to reach target BP. In either strategy additional drugs can be added provided the calcium antagonist is retained in the calcium antagonist care strategy and calcium antagonists are omitted in the non-calcium antagonist care strategy.

The study is organized into 15 international regions with about 1,500 study investigators randomizing approximately 22,000 patients who will be treated for at least two years. The primary response variable is the occurrence of adverse outcome, defined as any of the following events: all cause mortality, nonfatal MI or nonfatal stroke. A number of secondary response variables, including newly diagnosed diabetes will also be evaluated.

The primary objective of this trial is to examine the hypothesis that the risk for adverse outcomes (all cause mortality, nonfatal MI or nonfatal stroke) in hypertensive patients with CAD is at least equivalent during treatment of hypertension with a calcium antagonist strategy when compared with a non-calcium antagonist strategy.

Unique features of INVEST are, in addition to its size and international scope, its design to mimic standard clinical practice and its all electronic online data entry, drug distribution system, study management system, and electronic physician compensation. This system will permit the entire trial to be conducted via the Internet. This design is believed to be a forerunner of clinical trials research for the future.

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female

- Age 50 to no upper limit

- Hypertension documented according to the 6th report of the Joint National Committee on

Detection and Evaluation of the treatment of high BP (JNC VI) and the need for drug therapy (previously documented hypertension in patients currently taking antihypertensive agents is acceptable)

- Documented CAD (e. g., classic angina pectoris (stable angina pectoris; Heberden angina

pectoris), myocardial infarction three or more months ago, abnormal coronary angiography, or concordant abnormalities on two different types of stress tests)

- Willingness to sign informed consent

Exclusion Criteria:

- Unstable angina, angioplasty, coronary artery bypass graft surgery (CABG) or stroke

within one month. Patients taking beta blockers after myocardial infarction are excluded if study enrollment is planned within 12 months of myocardial infarction. No time limitation if not taking beta-blocker.

- Use of a ß-blocker within past two weeks

- Patients without a pacemaker and any of the following:

- Sinus bradycardia (< 50 beats/min.)

- Sick sinus syndrome

- Atrioventricular (AV)-block of more than 1st degree

- Documented contraindication to verapamil; documented contraindication to both atenolol

and hydrochlorothiazide

- Atrial fibrillation/flutter with Wolff-Parkinson-White (WPW)-Syndrome

- Severe heart failure (New York Heart Association [NYHA] IV).

- Concomitant illnesses (e. g., severe renal failure [Serum creatinine ≥4. 0 mg/dl],

severe hepatic failure or known cirrhosis, etc.) which may affect outcome variables or where life expectancy is two years or less or which are likely to require frequent hospitalizations and/or treatment adjustments.

- Patients with psychiatric, cognitive, or social (e. g., alcoholism, etc.) conditions

that would interfere with giving consent or cooperating or remaining available for follow-up for two years.

University of Florida, Gainesville, Florida 32610-0277, United States

Starting date: September 1997
Ending date: February 2003
Last updated: July 26, 2006