INVEST: INternational VErapamil SR Trandolapril STudy

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00133692
First received: August 22, 2005
Last updated: September 16, 2011
Last verified: August 2010
  Purpose

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 Intervention Phase
Hypertension
Coronary Artery Disease
Drug: Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ)
Drug: Atenolol/HCTZ/Trandolapril
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: INternational VErapamil SR Trandolapril STudy

Resource links provided by NLM:


Further study details as provided by University of Florida:

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

Estimated Enrollment: 22000
Study Start Date: September 1997
Estimated Study Completion Date: February 2003
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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
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: NCT00133692

Locations
United States, Florida
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
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00133692     History of Changes
Other Study ID Numbers: INVEST
Study First Received: August 22, 2005
Last Updated: September 16, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Hypertension
Coronary Artery Disease
INVEST
Diabetes
Verapamil SR
Trandolapril
Atenolol
HCTZ

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Hypertension
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Vascular Diseases
Atenolol
Hydrochlorothiazide
Trandolapril
Verapamil
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Calcium Channel Blockers
Cardiovascular Agents
Diuretics
Enzyme Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 23, 2014