Treatment of Sickle Cell Patients Hospitalized in Pain Crisis With Prophylactic Dose Low-molecular-weight Heparin (LMWH) Versus Placebo
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.
Sickle Cell Disease
|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|
- 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.
- 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.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||July 2014|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Normal saline solution
Normal saline solution, administered by nursing staff once daily
5000 unites subcutaneously, Other Name: Fragmin
Low molecular weight heparin (LMWH), 5000 unites subcutaneously, administered by nursing staff once daily, Other Name: Fragmin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01419977
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Nirmish Shah, MD||Duke University|