A Safety Study of Eptifibatide in Patients With Sickle Cell Disease
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase I/II Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Eptifibatide as Treatment for Acute Pain Episodes in Sickle Cell Disease|
- 1) Major Bleeding Episodes [ Time Frame: Up to 35 days ] [ Designated as safety issue: Yes ]Major bleeding episodes are defined as any episode, such as gastrointestinal bleeding or intracranial bleed that typically leads to hospitalization or other prolonged bleeding requiring a blood transfusion
- Change in Platelet Count [ Time Frame: Up to 35 days ] [ Designated as safety issue: Yes ]Change in platelet counts occurring anytime from randomization up to day 35 (final follow-up visit).
- Effect of Eptifibatide on Duration of Acute Pain Episodes [ Time Frame: Up to 7 days ] [ Designated as safety issue: No ]
The duration of the pain episode will be defined as the time from randomization to termination of the pain episode. The pain episode will be considered terminated when the patient states that the crisis is resolved (defined as being ready to go home on oral analgesics) or all of the following criteria are met:
- Pain relief (pain scores ≤ 40) maintained for at least 2 consecutive readings (assessed using a visual analog scale with measurements from 0 - 100, where 0 is no pain and 100 is worst imaginable pain).
- No parenteral analgesics have been administered for at least 12 hours.
- Ability to walk normally (unless he/she was unable to walk for some other reason prior to the crisis onset).
- Effect of Eptifibatide on Duration of Hospitalization [ Time Frame: Up to 7 days ] [ Designated as safety issue: No ]The duration of hospitalization will be defined as the period from randomization to the time an order for discharge from the hospital is written.
|Study Start Date:||January 2009|
|Study Completion Date:||March 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
As soon as eligible patients are identified and provide consent to participate in the study, patients randomized to the eptifibatide arm will receive two 180 mcg/kg boluses of eptifibatide 10 minutes apart (i.e., a double bolus), followed by a continuous infusion at 2 mcg/kg/min for 6 hours.
Patients randomized to eptifibatide will receive two 180 mcg/kg boluses of eptifibatide 10 minutes apart (i.e., a double bolus), followed by a continuous infusion at 2 mcg/kg/min for 6 hours.
Other Name: Integrilin
Placebo Comparator: 2
As soon as eligible patients are identified and provide consent to participate in the study, patients randomized to the placebo arm will receive a saline solution delivered at a volume and rate identical to that of the active drug.
Patients randomized to the placebo arm will receive a saline solution delivered at a volume and rate identical to that of the active drug.
Sickle cell disease has been referred to both as a condition associated with increased risk of blood clots and increased inflammation. Despite the abundant laboratory evidence of abnormal blood clotting and inflammation, the contribution of these changes to the problems experienced by patients with sickle cell disease remains uncertain. In additional to abnormal blood clotting, platelets (small blood cells that help blood clotting) are more activated in sickle cell disease patients compared to healthy patients without this disease.
In addition, when sickle cell disease patients experience a painful crisis, there is evidence that the platelet activation and abnormal blood clotting increase even further. Activated platelets release a substance called cluster of designation 40 ligand, which can increase how sticky the lining of blood vessels are and can increase the abnormal blood clotting. The level of cluster of designation 40 ligand is much higher in sickle cell disease patients compared to healthy individuals without this disease. In addition, the levels increase even further when sickle cell patients are experiencing a painful crisis.
Painful crisis represent the most common clinical problem in sickle cell disease, and are largely responsible for making the lives of these patients so unpredictable. However, the treatment of these painful crisis remains inadequate, consisting mainly of strong pain medications. In this study, we will evaluate the safety of eptifibatide in sickle cell patients and how well it works during the course of painful crises. At the completion of this trial, we will have an improved understanding of the contribution of platelet activation and inflammation to the problems in sickle cell disease.
The overall hypothesis that we seek to test is that increased platelet activation and the resultant inflammatory responses are important contributors to the problems of sickle cell disease. We believe that by decreasing platelet stickiness, and the release of mediators of inflammation and abnormal blood clotting, eptifibatide will affect the clinical course of complications in this disease.
If the results from our study support the hypothesis that eptifibatide is safe and effective in this population, we plan on carrying out larger studies to more definitively evaluate the safety of eptifibatide and how well it works in the treatment and/or prevention of painful crises in sickle cell disease.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00834899
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599-7305|
|Principal Investigator:||Kenneth I Ataga, MD||University of North Carolina, Chapel Hill|