Treatment of Sickle Cell Patients Hospitalized in Pain Crisis With Prophylactic Dose Low-molecular-weight Heparin (LMWH) Versus Placebo

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eisai Limited
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01419977
First received: August 17, 2011
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

Sickle cell disease (SCD) is one of the most common inherited diseases worldwide and exhibits highest frequency in people of African descent. Patients with SCD currently have few treatment options, with hydroxyurea being the only medication approved to reduce the frequency of vaso-occlusive crisis (VOC) and prevent other SCD complications such as acute chest syndrome. Once patients develop VOC, hospitalizations aim to alleviate pain; no specific therapy is currently available to otherwise affect the course of the VOC. However, there has been increasing interest in the role of coagulation in the pathogenesis of SCD. The investigators hypothesize that low dose anticoagulant therapy, such as prophylactic dose low-molecular-weight heparin (LMWH), could be a novel way to ameliorate the vaso-occlusive process and thereby hasten the resolution of pain.


Condition Intervention Phase
Sickle Cell Disease
Vaso-occlusive Crisis
Drug: Placebo
Drug: Dalteparin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Placebo Controlled Treatment of Sickle Cell Patients Hospitalized in Pain Crisis With Prophylactic Dose LMWH Versus Placebo

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Reduction of hypercoagulable markers [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Patients will have D-dimer, thrombin-antithrombin complex, prothrombin fragment 1.2 and thrombin generation assay performed for samples drawn on Day 1, 3, and 5.


Secondary Outcome Measures:
  • Reduction in clinical pain scores [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Patients will have twice daily pain scores performed and time needed to reduce pain score by 2 will be compared.


Enrollment: 34
Study Start Date: May 2011
Estimated Study Completion Date: July 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Normal saline solution
Drug: Placebo
Normal saline solution, administered by nursing staff once daily
Experimental: Dalteparin
5000 unites subcutaneously, Other Name: Fragmin
Drug: Dalteparin
Low molecular weight heparin (LMWH), 5000 unites subcutaneously, administered by nursing staff once daily, Other Name: Fragmin

Detailed Description:

This is a double blind prospective randomized placebo controlled study with an enrollment target of 100 patients. All subjects with SCD that meet inclusion criteria while inpatient, will be eligible for the study and randomized to receive prophylactic LMWH or placebo. Treatment with either LMWH (dalteparin 5000 IU subcutaneously daily) or placebo will occur for the initial 7 days of hospitalization. Randomization will occur within Investigational Drug Services, which will dispense and label medications to all patients. All patients will be followed throughout their hospitalization as well as in the outpatient clinic. The initial blood sample will be obtained within 36 hours of admission.

Following randomization, blood will be drawn to perform: D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and Thrombin Generation Assay (TGA). Blood will be drawn as an inpatient (at admission, day 3, and day 5), as well as during a single outpatient follow-up visit two weeks post discharge. Patients with prolonged hospitalization will only have blood drawn on admission, day 3, and day 5, with a final blood draw as an outpatient (at least 14 days after discharge). Treatment by prophylactic LMWH or placebo will occur for the initial 7 days of hospitalization or until discharge.

Clinical pain scores will be performed twice daily throughout for the initial 7 days of hospitalization of all patients. The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other. The VAS test will be administered by the same blinded study coordinator or PI throughout the study, using standardized instructions. Pain will also be assessed during the follow up outpatient visit (to confirm patient's pain has returned to their baseline).

Patients will be recommended to follow up in outpatient clinic approximately 2-4 week following hospitalization. At this time, patients will be examined, have their clinical pain score determined, and have final blood draw for testing as detailed above. Should patients not return within 4 weeks, patient will be contacted by phone to determine their clinical status.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented HgbSS or HgbS-beta0 thalassemia by previous hemoglobin electrophoresis,
  • age greater than 18 years old, and
  • admit diagnosis of vaso-occlusive crisis.

Labs must be drawn within 36 hours of admission and randomization to treatment arm must occur during this time.

Exclusion Criteria:

  • End stage renal disease (creatinine >3.0 mg/dL),
  • use of antiplatelet or anticoagulation medication for an alternative indication,
  • use of steroids or immunosuppressive medications,
  • platelet count less than 100 X 109/L,
  • history or development of heparin induced thrombocytopenia, packed red blood cell transfusion in the past one month, or
  • recent hospitalization with discharge within the past 1 week.

Patients with re-admissions will not be enrolled again and will have no further samples drawn.

  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: NCT01419977

Locations
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Eisai Limited
Investigators
Principal Investigator: Nirmish Shah, MD Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01419977     History of Changes
Other Study ID Numbers: Pro00023305
Study First Received: August 17, 2011
Last Updated: June 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
sickle cell disease
vaso-occlusive crisis
anticoagulation

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014