A Safety Study of Eptifibatide in Patients With Sickle Cell Disease

This study has been terminated.
(Slow accrual and no cost extension not approved by NHLBI)
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00834899
First received: January 31, 2009
Last updated: May 22, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Sickle Cell Disease
Drug: Eptifibatide
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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:

    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 [ 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.


Enrollment: 13
Study Start Date: January 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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.
Drug: Eptifibatide
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.
Drug: Placebo
Patients randomized to the placebo arm will receive a saline solution delivered at a volume and rate identical to that of the active drug.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00834899

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599-7305
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Kenneth I Ataga, MD University of North Carolina, Chapel Hill
  More Information

No publications provided by University of North Carolina, Chapel Hill

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00834899     History of Changes
Other Study ID Numbers: 1 R21 HL091265-01A1
Study First Received: January 31, 2009
Results First Received: February 24, 2013
Last Updated: May 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Sickle cell disease
Pain crisis
Acute pain episode
Eptifibatide
Antiplatelet therapy
Safety
Treatment

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Eptifibatide
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014