Sildenafil for Prevention of Cerebral Vasospasm

Study Overview
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Brief Summary
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A Randomized Clinical Trial with security and dose testing of Sildenafil Citrate in patients with subarachnoid hemorrhage due to a rupture of a cerebral aneurism for prevention of cerebral vasospasm. The cerebral vasospasm is a decrease in blood flow that occurs when the intracranial vessels lose their capability of self-control of dilations and contractions. Patients with subarachnoid hemorrhage without neurological deficits who underwent endovascular or surgical correction of the aneurysm can participate in this trial. They will be randomized to a daily doses of 75 mg of Sildenafil, 150 mg of Sildenafil or Placebo from the third to the 14th day post bleeding. Today there is no proven clinical treatment for prevention of cerebral vasospasm.

Official Title
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Sildenafil for Prevention of Cerebral Vasospasm Secondary to Subarachnoid Haemorrhage - Phase II Randomized Clinical Trial

Conditions
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Subarachnoid Hemorrhage, Cerebral Vasospasm, Rupture of Intracranial Aneurysm

Intervention / Treatment
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* Drug: Placebo
* Drug: Sildenafil Citrate, 25 mg, 3 times a day.
* Drug: Sildenafil Citrate 50 mg, 3 times a day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 20 and 80 years old Subarachnoid hemorrhage confirmed by CT with Fisher III or IV criteria (blood in cisterns larger than 1 mm with or without blood in the ventricular system). Aneurysm detected in the conventional angiography, or angio-CT or angio - MRI. Patient underwent surgery for clipping or endovascular treatment in the first 72 hours after the ictus. Consent form signed by the patient or legal responsible. Exclusion Criteria: Patient (or legal responsible) refuses to participate. Impossibility to collect consent form. Hemodynamical instability. Previous cardiac ischemic disease. History of cardiac arrhythmia within the last 6 months. History of Retinitis Pigmentosa. Previous use of drugs witch can interact with sildenafil (specially nitrates). Pregnancy. Known hypersensibility to Sildenafil.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo: soluble blue pigment<br>Soluble blue pigment for placebo controlling. | Drug: Placebo<br>* Soluble blue pigment, 3 times a day, from the third to the 14th day after subarachnoid hemorrhage.<br>|
| Experimental: Sildenafil, 75mg daily<br>Sildenafil citrate, 75 mg daily divided in 3 doses. From third to 14th day after subarachnoid hemorrhage. | Drug: Sildenafil Citrate, 25 mg, 3 times a day.<br>* Sildenafil Citrate 25 mg, 3 times a day (TID)from the third to the 14 day after subarachnoid hemorrhage.<br>* Other names: Viagra;|
| Experimental: Sildenafil, 150 mg daily<br>Sildenafil citrate, 150 mg daily divided in 3 doses from third to 14th day after subarachnoid hemorrhage. | Drug: Sildenafil Citrate 50 mg, 3 times a day<br>* Sildenafil Citrate 25 mg, 3 times a day (TID)from the third to the 14 day after subarachnoid hemorrhage.<br>* Other names: Viagra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New neurological Deficit | Development of clinical symptoms suggestive of vasospasm, which are: afasia, hemiparesis, disorientation, or worsening of consciousness without hydrocephalus or expanding cloth. To access level of consciousness we will use the Glasgow Coma Scale. | From third to 14th day post subarachnoid hemorrhage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcranial Ecodoppler | Signs of vasospasm in in transcranial ecodoppler. | From the third to the 14th day after subarachnoid hemorrhage | 
| Mortality | General mortality (for any causes). | From the third to the 14th day before subarachnoid hemorrhage. | 
| Side effects | Drug side effect: hypotension, visual blurring, nasal congestion, angina pectoris, asthma crisis, AV block, digestive bleeding, and priapism. | From the third to the 14th day after subarachnoid hemorrhage. | 
| Time to discharge | Time to discharge (period of hospital stay). | From the third day after subarachnoid hemorrhage to discharge. | 
| Rankin Scale | Modified Rankin scale at discharge. | At discharge from the hospital. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aneurysm, Vasospasm, sildenafil, Viagra