A Safety Study of Eptifibatide in Patients With Sickle Cell Disease

Phase 1

Terminated

• Conditions: Sickle Cell Disease
• Interventions: Drug: Eptifibatide; Drug: Placebo

• Registration Number: NCT00834899
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-31
• Study First Submitted QC: 2009-01-31
• Study First Posted: 2009-02-03
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Status Verified: 2013-02
• Results First Submitted: 2013-02-24
• Results First Submitted QC: 2013-05-22
• Last Update Submitted: 2013-05-22
• Results First Posted: 2013-06-27
• Last Update Posted: 2013-06-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

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)

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Eptifibatide	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.
2	Placebo	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.

Primary Outcome Measures

Name	Time	Method
1) Major Bleeding Episodes	Up to 35 days	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	Up to 35 days	Change in platelet counts occurring anytime from randomization up to day 35 (final follow-up visit).

Secondary Outcome Measures

Name	Time	Method
Effect of Eptifibatide on Duration of Acute Pain Episodes	Up to 7 days	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: 1. 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).; 2. No parenteral analgesics have been administered for at least 12 hours.; 3. 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	Up to 7 days	The duration of hospitalization will be defined as the period from randomization to the time an order for discharge from the hospital is written.

Trial Locations

Locations (1)

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States