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Stroke - Clinical Trials

Clinical Trials

Clinical research is usually conducted in a series of trials that become progressively larger. A phase I clinical trial is directly built upon the lessons learned from basic and animal research and is used to test the safety of therapy for a particular disease and to estimate possible efficacy in a few human subjects. A phase II clinical trial usually involves many subjects at several different centers and is used to test safety and possible efficacy on a broader scale, to test different dosing for medications or to perfect techniques for surgery, and to determine the best methodology and outcome measures for the bigger phase III clinical trial to come.

A phase III clinical trial is the largest endeavor in clinical research. This type of trial often involves many centers and many subjects. The trial usually has two patient groups who receive different treatments, but all other standard care is the same and represents the best care available. The trial may compare two treatments, or, if there is only one treatment to test, patients who do not receive the test therapy receive instead a placebo. The patients are told that the additional treatment they are receiving may be either the active treatment or a placebo. Many phase III trials are called double-blind, randomized clinical trials. Double-blind means that neither the subjects nor the doctors and nurses who are treating the subjects and determining the response to the therapy know which treatment a subject receives. Randomization refers to the placing of subjects into one of the treatment groups in a way that can’t be predicted by the patients or investigators. These clinical trials usually involve many investigators and take many years to complete. The hypothesis and methods of the trial are very precise and well thought out. Clinical trial designs, as well as the concepts of blinding and randomization, have developed over years of experimentation, trial, and error. At the present time, researchers are developing new designs to maximize the opportunity for all subjects to receive therapy.

Most treatments for general use come out of phase III clinical trials. After one or more phase III trials are finished, and if the results are positive for the treatment, the investigators can petition the FDA for government approval to use the drug or procedure to treat patients. Once the treatment is approved by the FDA, it can be used by qualified doctors throughout the country. The back packet of this brochure contains cards with information on some of the many stroke clinical trials the NINDS supports or has completed.


Trial Name Mode Selection Trial in Sinus Node Dysfunction (MOST)
Duration 1995 to 2000
Recruitment Status Currently Recruiting
Age Limit Any Age

Background

Disease(s) or condition(s) being studied in this trial:

Arrhythmia, Cardiovascular Diseases, Cerebrovascular Disorders, Heart/Vascular Diseases, Sick Sinus Syndrome, Stroke.

For additional information on the disease(s) or condition(s) being studied in this trial, click here

Permanent pacing is estimated to cost one billion dollars annually in health care costs in the United States. Initially, pacing was primarily confined to ventricular pacing with limited sensing, programming and pacing capacity. Tremendous growth has occurred in pacing technology, making available dual chamber pacing with sophisticated sensing, pacing, and rate control. These more advanced pacemakers are more costly and complicated to place surgically.

One of the most common indications for pacing is sick sinus syndrome. Initial therapy is usually medical to inhibit the tachyarrhythmias (most commonly paroxysmal atrial fibrillation). However, if symptomatic bradycardia results, then permanent pacing is commonly employed. The appropriate type of pacing in this setting is not clearly defined and is controversial.

The development of atrioventricular pacing was principally aimed at improving cardiac hemodynamics and creating a more physiological heart rate control. Hemodynamic studies have clearly shown the benefit of this approach in many patients, particularly those with decreased left ventricular compliance in whom atrial activity contributes significantly to cardiac output. Lack of synchronization between the upper and lower chambers of the heart caused by pacing the ventricle alone can result in a constellation of symptoms commonly referred to as "pacemaker syndrome".

The underlying mechanisms by which dual chamber pacing is purported to improve outcome is straightforward; in patients with normal sinus rhythm, cardiac output is improved by 15 to 30 percent. In addition, a number of retrospective studies that have compared single chamber with atrial-based or dual chamber pacing have suggested that the latter may prevent adverse clinical events such as atrial fibrillation, congestive heart failure, cerebral vascular accidents, and death. While none of these studies was a randomized trial, the literature is consistent with a concept that dual mode pacing results in improved hemodynamics and a more favorable outcome in patients with sick sinus syndrome. However, the data do not provide definitive answers because of small sample sizes and methodological problems. A major problems with all previous studies is probable selection bias favoring implantation of dual chamber devices in younger, healther patients.

Several small studies have compared functional status and other quality of life measures between single and dual chamber pacing modes and have suggested better quality of life outcomes for the dual chamber mode. Again, these conclusions are severly hampered by the sample sizes, the lack of random assignment or adequate statistical adjustment to control for confounding, use of outdated and/or invalid measures, and potential response bias due to awareness of mode assignment.

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