A Safety Study of Eptifibatide in Patients With Sickle Cell Disease
A Safety Study of Eptifibatide in Patients With Sickle Cell Disease
This study will evaluate the safety of eptifibatide in sickle cell patients and how well it
 works during the course of painful crises. 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. Sickle cell disease has been referred to
 both as a condition associated with increased risk of blood clots and increased inflammation.
 A painful crisis represents the most common cli nical problem in sickle cell disease, but the
 treatment of these crises remains inadequate.
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.
Inclusion Criteria:

 1. Age between 18 and 55 years

 2. Have confirmed diagnosis of sickle cell anemia or sickle beta zero thalassemia

 3. Have a serum creatinine </= 1.2 mg/dl

 4. Have serum transaminase values < 3 times upper limits of normal

 5. Have a platelet count >/= 150 x 10^9/L

 6. Have normal baseline coagulation profile

 7. Sudden onset of pain involving one or more sites and typical of usual pain episodes

 8. Have adequate intravenous access

 9. Be able to understand the requirements of the study and be willing to give informed
 consent

 10. Women of child-bearing age must be practicing (and will continue to practice for the
 course of the study) an adequate method of contraception (oral contraception,
 depo-provera, bilateral tubal ligation or barrier method)

 Exclusion Criteria:

 1. Have a baseline hemoglobin < 6.0 gm/dl

 2. Have a history of major gastrointestinal bleeding or a bleeding diathesis

 3. Have an ongoing episode of acute chest syndrome

 4. Have a past history of clinically overt stroke(s)

 5. Have severe hypertension (systolic blood pressure > 200mmHg and/or diastolic BP
 >110mmHg) not adequately controlled on hypertensive medication

 6. Have had major surgery within the six weeks preceding enrollment

 7. Are pregnant or breastfeeding

 8. Are on chronic anticoagulation or antiplatelet (including non-steroidal
 anti-inflammatory drugs) therapy

 9. Have a history of metastatic cancer

 10. Are on a chronic transfusion program or have received a blood transfusion in the prior
 8 weeks

 11. Have a positive urine toxicology screen for phencyclidine, cocaine or amphetamines.

 12. Have a history of alcohol abuse

 13. Have received any investigational drugs within the past 4 weeks.