INVEST: INternational VErapamil SR Trandolapril STudy
Study Details
Study Description
Brief Summary
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
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.
Study Design
Outcome Measures
Primary Outcome Measures
- First occurrence of death or nonfatal myocardial infarction (MI) or nonfatal stroke []
Secondary Outcome Measures
- 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 []
Eligibility Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Florida | Gainesville | Florida | United States | 32610-0277 |
Sponsors and Collaborators
- University of Florida
- Abbott
Investigators
- Principal Investigator: Carl J Pepine, MD, University of Florida
Study Documents (Full-Text)
None provided.More Information
Publications
- Conti CR, Cooper-DeHoff RM. How will INVEST and other hypertension trials change clinical practice? Clin Cardiol. 2001 Nov;24(11 Suppl):V24-9.
- Cooper-DeHoff R, Handberg E, Heissenberg C, Johnson K. Electronic prescribing via the internet for a coronary artery disease and hypertension megatrial. Clin Cardiol. 2001 Nov;24(11 Suppl):V14-6.
- Erdine S, Handberg EM, Kolb B. Characteristics of patients with coronary artery disease and hypertension: a report from INVEST. Clin Cardiol. 2001 Nov;24(11 Suppl):V6-8.
- Keltai M, Johnson JA, Kowey PR, Ried LD, Tueth M. INVEST substudies: design and patient characteristics. Clin Cardiol. 2001 Nov;24(11 Suppl):V9-11.
- Kolloch RE. INVEST: results of combined strategies to control blood pressure. Clin Cardiol. 2001 Nov;24(11 Suppl):V12-3.
- Marks R, Bristol H, Conlon M, Pepine CJ. Enhancing clinical trials on the internet: lessons from INVEST. Clin Cardiol. 2001 Nov;24(11 Suppl):V17-23.
- Pepine CJ, Cooper-Dehoff RM. Cardiovascular therapies and risk for development of diabetes. J Am Coll Cardiol. 2004 Aug 4;44(3):509-12. Review.
- Pepine CJ, Handberg EM. The vascular biology of hypertension and atherosclerosis and intervention with calcium antagonists and angiotensin-converting enzyme inhibitors. Clin Cardiol. 2001 Nov;24(11 Suppl):V1-5.
- Pepine CJ, Handberg-Thurmond E, Marks RG, Conlon M, Cooper-DeHoff R, Volkers P, Zellig P. Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension. J Am Coll Cardiol. 1998 Nov;32(5):1228-37.
- Questions and answers related to the INternational VErapamil SR/trandolapril STudy (INVEST). Clin Cardiol. 2001 Nov;24(11 Suppl):V30.
- Reynolds NA, Wagstaff AJ, Keam SJ. Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension. Drugs. 2005;65(13):1893-914. Review.
- INVEST