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AzTrials

HypertensionPhase 4NCT00133692

INVEST: INternational VErapamil SR Trandolapril STudy

A Phase 4 study testing Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ) and Atenolol/HCTZ/Trandolapril in people with Hypertension and Coronary Artery Disease, run by University of Florida at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Hypertension, Coronary Artery Disease
What is being tested?
Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ) and Atenolol/HCTZ/Trandolapril
How many people
22,000 participants
Where
1 siteUnited States
Study dates
Sep 1997to Feb 2003
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Florida

    Gainesville, Florida, 32610-0277

Other trials in United States

About this study

Official title: INternational VErapamil SR Trandolapril STudy

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).

Read the 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.

Being tested
Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ), Atenolol/HCTZ/Trandolapril
Keywords
Hypertension, Coronary Artery Disease, INVEST, Diabetes, Verapamil SR, Trandolapril, Atenolol, HCTZ
Medical subject headings
Hypertension, Coronary Artery Disease, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ)Drug

  • Atenolol/HCTZ/TrandolaprilDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. First occurrence of death or nonfatal myocardial infarction (MI) or nonfatal stroke

Secondary outcomes (12)

  1. Death

  2. Nonfatal MI

  3. Nonfatal stroke

  4. Newly diagnosed diabetes

  5. BP control

  6. Cancer

  7. Gastrointestinal (GI) bleeding

  8. Alzheimer's Disease

  9. Parkinson's Disease

  10. Cardiovascular (CV) hospitalizations

  11. Quality of life

  12. Compliance

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2005 (estimated)
  2. Study startSep 1997
  3. Study completionFeb 2003

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
22,000 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00133692
Sponsor's protocol ID
INVEST
Status last verified
Aug 2010
First submitted
22 Aug 2005
Last updated
20 Sep 2011
Results posted
No

Publications

  • 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. doi: 10.2165/00003495-200565130-00011.

    PubMed 16114984

  • Pepine CJ, Cooper-Dehoff RM. Cardiovascular therapies and risk for development of diabetes. J Am Coll Cardiol. 2004 Aug 4;44(3):509-12. doi: 10.1016/j.jacc.2004.03.071.

    PubMed 15358012

  • 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. doi: 10.1002/clc.4960241704.

    PubMed 11712776

  • 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. doi: 10.1002/clc.4960241703.

    PubMed 11712775

  • Questions and answers related to the INternational VErapamil SR/trandolapril STudy (INVEST). Clin Cardiol. 2001 Nov;24(11 Suppl):V30. No abstract available.

    PubMed 11712774

  • Conti CR, Cooper-DeHoff RM. How will INVEST and other hypertension trials change clinical practice? Clin Cardiol. 2001 Nov;24(11 Suppl):V24-9. doi: 10.1002/clc.4960241708.

    PubMed 11712773

  • 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. doi: 10.1002/clc.4960241707.

    PubMed 11712772

  • 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. doi: 10.1002/clc.4960241706.

    PubMed 11712771

  • Kolloch RE. INVEST: results of combined strategies to control blood pressure. Clin Cardiol. 2001 Nov;24(11 Suppl):V12-3. doi: 10.1002/clc.4960241705.

    PubMed 11712770

  • 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. doi: 10.1002/clc.4960241702.

    PubMed 11712769

  • 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. doi: 10.1016/s0735-1097(98)00423-9.

    PubMed 9809930

  • Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, Pepine CJ. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010 Jul 7;304(1):61-8. doi: 10.1001/jama.2010.884.

    PubMed 20606150

  • Denardo SJ, Messerli FH, Gaxiola E, Aranda JM Jr, Cooper-Dehoff RM, Handberg EM, Gong Y, Champion A, Zhou Q, Pepine CJ. Coronary revascularization strategy and outcomes according to blood pressure (from the International Verapamil SR-Trandolapril Study [INVEST]). Am J Cardiol. 2010 Aug 15;106(4):498-503. doi: 10.1016/j.amjcard.2010.03.056.

    PubMed 20691307

  • Denardo SJ, Gong Y, Nichols WW, Messerli FH, Bavry AA, Cooper-Dehoff RM, Handberg EM, Champion A, Pepine CJ. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Am J Med. 2010 Aug;123(8):719-26. doi: 10.1016/j.amjmed.2010.02.014.

    PubMed 20670726

  • Beitelshees AL, Navare H, Wang D, Gong Y, Wessel J, Moss JI, Langaee TY, Cooper-DeHoff RM, Sadee W, Pepine CJ, Schork NJ, Johnson JA. CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response. Circ Cardiovasc Genet. 2009 Aug;2(4):362-70. doi: 10.1161/CIRCGENETICS.109.857839. Epub 2009 Jun 3.

    PubMed 20031608

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Verapamil SR/Trandolapril/Hydrochlorothiazide (HCTZ) and Atenolol/HCTZ/Trandolapril in people with Hypertension and Coronary Artery Disease, run by University of Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

First occurrence of death or nonfatal myocardial infarction (MI) or nonfatal stroke. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00133692, which also lists 56 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2011.

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