Sickle Cell DiseasePhase 1/2NCT00834899
A Safety Study of Eptifibatide in Patients With Sickle Cell Disease
A Phase 1/2 study testing Eptifibatide in people with Sickle Cell Disease, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Eptifibatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Mar 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 18 and 55 years
- Have confirmed diagnosis of sickle cell anemia or sickle beta zero thalassemia
- Have a serum creatinine </= 1.2 mg/dl
- Have serum transaminase values < 3 times upper limits of normal
- Have a platelet count >/= 150 x 10^9/L
- Have normal baseline coagulation profile
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- Sudden onset of pain involving one or more sites and typical of usual pain episodes
- Have adequate intravenous access
- Be able to understand the requirements of the study and be willing to give informed consent
- 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)
Who cannot join
- Have a baseline hemoglobin < 6.0 gm/dl
- Have a history of major gastrointestinal bleeding or a bleeding diathesis
- Have an ongoing episode of acute chest syndrome
- Have a past history of clinically overt stroke(s)
- Have severe hypertension (systolic blood pressure > 200mmHg and/or diastolic BP >110mmHg) not adequately controlled on hypertensive medication
- Have had major surgery within the six weeks preceding enrollment
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- Are pregnant or breastfeeding
- Are on chronic anticoagulation or antiplatelet (including non-steroidal anti-inflammatory drugs) therapy
- Have a history of metastatic cancer
- Are on a chronic transfusion program or have received a blood transfusion in the prior 8 weeks
- Have a positive urine toxicology screen for phencyclidine, cocaine or amphetamines.
- Have a history of alcohol abuse
- Have received any investigational drugs within the past 4 weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599-7305
About this study
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
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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Eptifibatide, Placebo
- Keywords
- Sickle cell disease, Pain crisis, Acute pain episode, Eptifibatide, Antiplatelet therapy, Safety, Treatment
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EptifibatideDrug
Also called Integrilin
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.
PlaceboDrug
Patients randomized to the placebo arm will receive a saline solution delivered at a volume and rate identical to that of the active drug.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 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. Receives: Drug: Eptifibatide |
| 2 | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
1) Major Bleeding Episodes
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
Measured: Up to 35 days
Change in Platelet Count
Change in platelet counts occurring anytime from randomization up to day 35 (final follow-up visit).
Measured: Up to 35 days
Secondary outcomes (2)
Effect of Eptifibatide on Duration of Acute Pain Episodes
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).
Measured: Up to 7 days
Effect of Eptifibatide on Duration of Hospitalization
The duration of hospitalization will be defined as the period from randomization to the time an order for discharge from the hospital is written.
Measured: Up to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionMar 2012
- Study completionMar 2012
Why it stopped: Slow accrual and no cost extension not approved by NHLBI
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kenneth I Ataga, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00834899
- Sponsor's protocol ID
- 1R21HL091265-01A1
- Status last verified
- Feb 2013
- First submitted
- 31 Jan 2009
- Last updated
- 27 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Desai PC, Brittain JE, Jones SK, McDonald A, Wilson DR, Dominik R, Key NS, Parise LV, Ataga KI. A pilot study of eptifibatide for treatment of acute pain episodes in sickle cell disease. Thromb Res. 2013 Sep;132(3):341-5. doi: 10.1016/j.thromres.2013.08.002. Epub 2013 Aug 8.
PubMed 23973010
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00834899
- Acronym / sponsor ID
- 1R21HL091265-01A1
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle cell disease, Pain crisis, Acute pain episode, Eptifibatide, Antiplatelet therapy, Safety, Treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual and no cost extension not approved by NHLBI
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 3 Feb 2009 (estimated)
- Results
- Posted 27 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: EptifibatideAs 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 comparator | Drug: PlaceboAs 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Age between 18 and 55 years
- Have confirmed diagnosis of sickle cell anemia or sickle beta zero thalassemia
- Have a serum creatinine </= 1.2 mg/dl
- Have serum transaminase values < 3 times upper limits of normal
- Have a platelet count >/= 150 x 10^9/L
Key exclusion criteria (13 listed)
- Have a baseline hemoglobin < 6.0 gm/dl
- Have a history of major gastrointestinal bleeding or a bleeding diathesis
- Have an ongoing episode of acute chest syndrome
- Have a past history of clinically overt stroke(s)
- Have severe hypertension (systolic blood pressure > 200mmHg and/or diastolic BP >110mmHg) not adequately controlled on hypertensive medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EptifibatideAlso: IntegrilinPatients 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. | Drug | 1 |
| PlaceboPatients randomized to the placebo arm will receive a saline solution delivered at a volume and rate identical to that of the active drug. | Drug | 2 |
Primary outcome
1) Major Bleeding Episodes
Time frame: 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
Time frame: Up to 35 days
Change in platelet counts occurring anytime from randomization up to day 35 (final follow-up visit).
2 secondary outcomes
Effect of Eptifibatide on Duration of Acute Pain Episodes
Time frame: Up to 7 days
Effect of Eptifibatide on Duration of Hospitalization
Time frame: Up to 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23973010Desai PC, Brittain JE, Jones SK, McDonald A, Wilson DR, Dominik R, Key NS, Parise LV, Ataga KI. A pilot study of eptifibatide for treatment of acute pain episodes in sickle cell disease. Thromb Res. 2013 Sep;132(3):341-5. doi: 10.1016/j.thromres.2013.08.002. Epub 2013 Aug 8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth I Ataga, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Eptifibatide in people with Sickle Cell Disease, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1) Major Bleeding Episodes (time frame: Up to 35 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00834899, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2013.