The main purpose of the study is to evaluate the efficacy and safety of the study drug known as prasugrel for the reduction of Vaso-Occlusive Crisis events in pediatric participants with sickle cell disease. The study will also investigate reduction in daily pain in children who have sickle cell disease.
The submission database was validated for data reported through the data cutoff date for the submission database lock (SDBL). The SDBL data cutoff was 17 July 2015 for all participants except for 2 in the youngest age group, for whom the SDBL data cutoff occurred on 08 August 2015. The data cutoff date for SDBL corresponds to the primary completion date for the study. The SDBL occurred on 31 August 2015. The study was stopped following SDBL and review of the topline information indicated that the primary and secondary efficacy endpoints were not met. Subsequently, the Sponsor requested that participants discontinue study drug immediately and that discontinuation visits for all active study participants be conducted as soon as feasible. After the data cutoff date for SDBL, the Sponsor continued to collect safety data through the final participants contact; some additional efficacy data were collected through the final visit. The last patient visit (LPV) occurred on 17 December 2015, which corresponds to the study completion date and led to the planned supplemental database lock (PSDBL) on 22 January 2016. This supplemental data base was originally designed to capture additional blinded and randomized information to enhance safety data for labeling should the study have been positive. The safety information contained in this record reflects the entire safety information and reflects the information from the supplemental data base lock in January of 2016. The efficacy information contained in this record reflects the information collected through primary completion date in the submission database. Primary analyses of the major efficacy objectives were repeated using the entire double-blind period data from the PSDBL and did not change the original conclusions and were consistent with the results from the original efficacy analyses included in the SDBL.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
341
Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC)
The VOC is a composite endpoint of painful crisis or acute chest syndrome. Events that occurred within 7 days from the prior event onset date were not counted as a new episode. Data collected through the primary completion date reported below.
Time frame: Randomization through 24 Months
Monthly Rate of Days With Pain
Monthly rate of days with pain was measured through participant diaries using a modified version of the Faces Pain Scale-Revised (FPS-R). Each day participants selected the face on the scale that reflected their worst pain related to sickle cell disease (SCD) on that day. This pain scale contains six faces corresponding to the pain intensity of 0, 2, 4, 6, 8 or 10, in which 0 denotes no pain and 10 denotes the worst pain possible. Any day the participant selected a face other than face 0 was considered a day with pain. Monthly rate of days with pain was calculated for each participant by summing the number of days reported with any pain divided by the number of non-missing diary entries completed in the month. A month was defined as 4 weeks (28 days).The monthly rate was set to missing if there were more than 14 missing entries for the FPS-R in a specific month. Data collected through the primary completion date are present below.
Time frame: Randomization through 9 Months
Monthly Mean in Faces Pain Scale-Revised Score
Each day participants selected the face on the FPS-R scale that reflected their worst pain related to sickle cell disease (SCD) on that day. Monthly mean in FPS-R score was calculated for each participant by summing the FPS-R score divided by the number of non-missing diary entries completed in the month. This pain scale contains six faces corresponding to the pain intensity of 0, 2, 4, 6, 8 or 10, in which 0 denotes no pain and 10 denotes the worst pain possible. A month was defined as 4 weeks (28 days). The monthly mean in FPS-R score was set to missing if there were more than 14 missing entries for the FPS-R in a specific month. Data collected through the primary completion date are presented below.
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Children's Hospital of Oakland
Oakland, California, United States
Stanford Univ Medical Center
Palo Alto, California, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Howard University Hospital
Washington D.C., District of Columbia, United States
Emory University
Atlanta, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Boston Children's Hospital
Boston, Massachusetts, United States
Childrens Hospital of Michigan
Detroit, Michigan, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
...and 40 more locations
Time frame: Randomization through 9 Months
Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis)
A painful crisis is defined as an onset of moderate to severe pain that lasts at least 2 hours for which there is no explanation other than vaso-occlusion and which requires therapy with oral or parenteral opioids, ketorolac, or other analgesics prescribed by a health care provider (HCP) in a medical setting such as a hospital, clinic, emergency room visit, or telephone management. The painful crisis that occurred within 7 days from the prior event onset date was not counted as a new episode. Data collected through the primary completion date are presented below.
Time frame: Randomization through 24 Months
Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations)
Hospitalization that occurred within 7 days of the prior event onset date were not counted as a new episode. Data collected through the primary completion date are presented below.
Time frame: Randomization through 24 Months
Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome)
Acute chest syndrome was defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray. Acute chest syndrome that occurred within 7 days of the prior event onset date was not counted as a new episode. Data collected through the primary completion date are presented below.
Time frame: Randomization through 24 Months
Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions)
RBC transfusions that occurred within 7 days of the prior event onset date were not counted as a new episode. Data collected through the primary completion date are presented below.
Time frame: Randomization through 24 Months
Monthly Rate of Days of Analgesic Use
Monthly rate of days of analgesic use was measured through participant diaries and was calculated for each participant by summing the number of days they reported analgesic use divided by the number of diary entries completed in the month. A month was defined as 4 weeks (28 days). The monthly rate was set to missing if there were more than 14 missing entries for analgesic use in a specific month. Data collected through the primary completion date are presented below.
Time frame: Randomization through 9 Months
Quarterly Rate of School Absence Due to Sickle Cell Pain
Quarterly rate of school absence due to sickle cell pain was measured through participant diaries and was calculated for each participant by summing the number of days with school absence due to sickle cell pain divided by the number of school dates in the quarter. A quarter was defined as 12 weeks. The quarterly rate was set to missing if there were more than 6 weeks of missing diary entries during a specific quarter. Data collected through the primary completion date are presented below.
Time frame: Randomization through 9 Months
Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke
Time frame: Randomization through 24 Months
Number of Days Hospitalized for VOC
The total length of hospitalization in days for VOC was calculated for each participant. Data collected through the primary completion date are presented below.
Time frame: Randomization through 24 Months
Time From Randomization to First and Second VOC
Data collected through the primary completion date are presented below.
Time frame: Randomization to First VOC and Second VOC respectively (up to 24 Months)
Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention
Medical intervention was defined as any medical evaluation resulting in therapy or further investigation, as determined by a trained medical professional. Data collected from the first dose of study medication through 10 days after last dose of study medication during the double blind study period are presented below.
Time frame: First Dose through 24 Months