Sildenafil (Viagra) Treatment of Subacute Ischemic Stroke
Stroke is the third leading cause of death in the United States and the leading cause of serious long-term disability. Approximately 50% of the 750,000 people affected by stroke each year have residual physical impairment. Treatment options for recovery are limited at this time. Sildenafil (Viagra) has demonstrated the capability of significantly improving recovery in several animal experiments of stroke. This study is aiming to establish the safety of treatment with sildenafil in people with stroke with the ultimate aim of testing its usefulness to improve recovery.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Study of Sildenafil (Viagra) Treatment of Subacute Ischemic Stroke|
- The maximum tolerated dose and toxicity profile of sildenafil treatment in patients with subacute ischemic stroke. [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
- The estimated efficacy of sildenafil in comparison with concurrent patients randomized assigned to usual care. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2005|
Orally administered sildenafil in addition to usual care.
Drug: Sildenafil (Viagra)
Dose escalation (one of the following): 25 mg daily for 2 weeks, 50 mg daily for 2 weeks, 75 mg daily for 2 weeks, 50 mg twice daily for two weeks, 50 mg AM and 75 mg PM for 2 weeks, 75 mg twice daily for 2 weeks, 75 mg in AM and 100 mg in PM for 2 weeks, 100 mg twice daily for 2 weeks.
Active Comparator: Usual post-stroke care
Usual post-stroke treatment including physical, occupational, and speech therapy.
Other: Usual care
Physical therapy, occupational therapy, speech therapy
Stroke is the third leading cause of death and the leading cause of serious long-term disability in the United States. Approximately 15-30% of stroke survivors are permanently disabled. Twenty eight percent of stroke patients are under age 65 which results in a loss of work income. While many restorative therapies are touted as promising for the treatment of ischemic stroke, to date none are approved for this purpose. Sildenafil (Viagra®), a phosphodiesterase type 5 inhibitor, has been shown to reduce mortality and improve the functional outcomes of young and aged rats when administered 24 hours and 7 days after stroke onset. Such results are encouraging and warrant further investigation in human stroke.
The specific aims of this study are to assess the safety of treating ischemic stroke patients with sildenafil (Viagra®) and to evaluate their outcomes at day 90. This will be a phase I dose-escalation study with cohort sizes of 12 patients (depending on the occurrence of serious adverse events). A total enrollment of 120 patients is planned. Patients who are between 4 and 7 days from stroke onset will receive 25, 50, 75, 100, 125, 150, 175, and 200 mg daily of sildenafil for a period of 14 days. Of the 120 patients, 24 will be randomly selected to receive standard treatment but will not receive sildenafil. All patients and physicians will be aware of treatment assignment. Evaluation of potential toxicity will be monitored throughout the course of treatment and during a formal visit at day 16 after initiation of treatment. Plasma monitoring of vascular endothelial growth factor (VEGF) will be made prior to treatment, at days 7, 16, 30, 60, and 90. Measurements of NIHSS scores, Rankin scores, and Barthel indices will be made at days 30, 60, and 90. Patients will also be assessed for color vision changes and sexual function during day 16 and day 90 visits. There will be every other day phone calls to patients while on treatment. The primary outcome measure will be death, recurrent stroke, and myocardial infarction during treatment. Exploratory analysis will include functional outcomes as measured on the neurological scales, and changes in VEGF levels in relation to clinical outcome.
The long-term objective is to identify a safe and easily administered treatment that improves functional outcome in patients with ischemic stroke.