Sickle Cell Disease
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGPrasugrel
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Daiichi Sankyo
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Have SCD \[homozygous sickle cell (HbSS) or hemoglobin (HbS) Beta\^0 thalassemia\] * Are participants with SCD who have had ≥2 episodes of vaso-occlusive crisis (VOC) in the past year * Have a body weight ≥19 kilograms (kg) and are ≥2 and \<18 years of age, inclusive at the time of screening * If participants are ≥2 and ≤16 years of age, must have had a transcranial Doppler within the last year
Exclusion criteria
* History of: transient ischemic attack (TIA)/ ischemic or hemorrhagic stroke, severe head trauma, intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm * History of abnormal or conditional \[velocity in middle or anterior cerebral, or internal carotid artery ≥170 centimeter per second (cm/sec)\] transcranial Doppler within the last year * History of, or are undergoing treatment with, chronic red blood cell (RBC) transfusion therapy * Are at an increased risk for bleeding complications * Are receiving chronic treatment with nonsteroidal anti-inflammatory drug (NSAID)s and cannot be switched to another analgesic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC) | Randomization through 24 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monthly Mean in Faces Pain Scale-Revised Score | Randomization through 9 Months | 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. |
| Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis) | Randomization through 24 Months | 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. |
| Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations) | Randomization through 24 Months | 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. |
| Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome) | Randomization through 24 Months | 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. |
| Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions) | Randomization through 24 Months | 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. |
| Monthly Rate of Days With Pain | Randomization through 9 Months | 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. |
| Quarterly Rate of School Absence Due to Sickle Cell Pain | Randomization through 9 Months | 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 to First Transient Ischemic Attack (TIA)/Ischemic Stroke | Randomization through 24 Months | — |
| Number of Days Hospitalized for VOC | Randomization through 24 Months | 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 From Randomization to First and Second VOC | Randomization to First VOC and Second VOC respectively (up to 24 Months) | Data collected through the primary completion date are presented below. |
| Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention | First Dose through 24 Months | 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. |
| Monthly Rate of Days of Analgesic Use | Randomization through 9 Months | 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. |
Countries
Belgium, Brazil, Canada, Egypt, Ghana, Italy, Kenya, Lebanon, Oman, Saudi Arabia, Turkey (Türkiye), United Arab Emirates, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Participants will be titrated from initial daily dose of 0.08 milligram per kilogram (mg/kg) of orally administered prasugrel monotherapy at randomization to a dose that will achieve a P2Y12 reaction units (PRU) level of 231 to 136, as measured by VerifyNow instrument. This corresponds to a range of platelet inhibition of approximately 30% to 60%. The maximum possible dose allowed is 0.12 mg/kg daily, not to exceed 10 mg daily. | 171 |
| Placebo Participants in this treatment group will receive daily orally administered placebo and will follow visit schedule identical to that in the active treatment group. | 170 |
| Total | 341 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Phase (DBP) | Adverse Event | 5 | 2 |
| Double-Blind Phase (DBP) | Death | 1 | 2 |
| Double-Blind Phase (DBP) | Entry Criteria Not Met | 2 | 0 |
| Double-Blind Phase (DBP) | Parent/Caregiver Decision | 5 | 2 |
| Double-Blind Phase (DBP) | Physician Decision | 2 | 0 |
| Double-Blind Phase (DBP) | Sponsor Decision | 148 | 149 |
| Double-Blind Phase (DBP) | Withdrawal by Subject | 6 | 11 |
| Open-Label Extension Phase (OLE) | Sponsor Decision | 3 | 0 |
Baseline characteristics
| Characteristic | Prasugrel | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 10.606 years STANDARD_DEVIATION 4.334 | 10.580 years STANDARD_DEVIATION 4.349 | 10.593 years STANDARD_DEVIATION 4.335 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 98 Participants | 192 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 75 Participants | 71 Participants | 146 Participants |
| Hydroxyurea Use at Baseline No | 94 participants | 94 participants | 188 participants |
| Hydroxyurea Use at Baseline Yes | 77 participants | 76 participants | 153 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 113 Participants | 109 Participants | 222 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 58 Participants | 58 Participants | 116 Participants |
| Region of Enrollment Belgium | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Brazil | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Egypt | 23 participants | 22 participants | 45 participants |
| Region of Enrollment Ghana | 29 participants | 28 participants | 57 participants |
| Region of Enrollment Italy | 7 participants | 7 participants | 14 participants |
| Region of Enrollment Kenya | 47 participants | 44 participants | 91 participants |
| Region of Enrollment Lebanon | 8 participants | 8 participants | 16 participants |
| Region of Enrollment Oman | 2 participants | 4 participants | 6 participants |
| Region of Enrollment Saudi Arabia | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Turkey | 20 participants | 22 participants | 42 participants |
| Region of Enrollment United Kingdom | 5 participants | 4 participants | 9 participants |
| Region of Enrollment United States | 23 participants | 25 participants | 48 participants |
| Sex: Female, Male Female | 87 Participants | 86 Participants | 173 Participants |
| Sex: Female, Male Male | 84 Participants | 84 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 148 / 170 | 154 / 170 | 1 / 3 |
| serious Total, serious adverse events | 100 / 170 | 106 / 170 | 0 / 3 |
Outcome results
Primary
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
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC) | 2.295 Number of Events per Participant-Year |
| Placebo | Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC) | 2.767 Number of Events per Participant-Year |
Comparison: The time to a recurrent episode of VOC was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model.p-value: 0.11795% CI: [0.66, 1.05]Andersen-Gill model
Secondary
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.
Time frame: Randomization through 9 Months
Population: All randomized participants who are 7 years or older and have both baseline and at least one post-baseline monthly outcome measure in any month. This is the Sickle cell population in which content validity has been established for the FPS-R.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Monthly Mean in Faces Pain Scale-Revised Score | 0.7116 Units on a Scale | Standard Error 0.0757 |
| Placebo | Monthly Mean in Faces Pain Scale-Revised Score | 0.6148 Units on a Scale | Standard Error 0.0753 |
p-value: 0.36595% CI: [-0.1132, 0.3068]Mixed Models Analysis
Secondary
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
Population: All randomized participants who are 4 years or older and have baseline and at least one post-baseline monthly outcome measure in any month. Diaries were only provided to participants 4 years and older.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Monthly Rate of Days of Analgesic Use | 24.270 Percentage of Days in a Month | Standard Error 2.29 |
| Placebo | Monthly Rate of Days of Analgesic Use | 22.757 Percentage of Days in a Month | Standard Error 2.337 |
p-value: 0.60295% CI: [-4.186, 7.213]Mixed Models Analysis
Secondary
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
Population: All randomized participants who are 7 years or older and have both baseline and at least one post-baseline monthly outcome measure in any month. This is the Sickle cell population in which content validity has been established for the FPS-R.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Monthly Rate of Days With Pain | 17.457 Percentage of Days in a Month | Standard Error 1.558 |
| Placebo | Monthly Rate of Days With Pain | 17.699 Percentage of Days in a Month | Standard Error 1.551 |
p-value: 0.91295% CI: [-4.564, 4.079]Mixed Models Analysis
Secondary
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
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome) | 0.112 Number of Events per Participant-Year |
| Placebo | Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome) | 0.115 Number of Events per Participant-Year |
p-value: 0.91695% CI: [0.48, 1.93]Andersen-Gill model
Secondary
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
Population: All randomized participants who were hospitalized for VOC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Number of Days Hospitalized for VOC | 12.9 Days | Standard Error 1.72 |
| Placebo | Number of Days Hospitalized for VOC | 12.0 Days | Standard Error 1.63 |
p-value: 0.66295% CI: [-3.31, 5.19]ANCOVA
Secondary
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
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations) | 1.064 Number of Events per Participant-Year |
| Placebo | Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations) | 1.126 Number of Events per Participant-Year |
p-value: 0.75995% CI: [0.65, 1.37]Andersen-Gill model
Secondary
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
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis) | 2.239 Number of Events per Participant-Year |
| Placebo | Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis) | 2.720 Number of Events per Participant-Year |
p-value: 0.10995% CI: [0.65, 1.04]Andersen-Gill Model
Secondary
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
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions) | 0.497 Number of Events per Participant-Year |
| Placebo | Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions) | 0.420 Number of Events per Participant-Year |
p-value: 0.54495% CI: [0.71, 1.91]Andersen-Gill model
Secondary
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
Population: All randomized participants who received at least one dose of drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention | 6.5 Percentage of Participants |
| Placebo | Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention | 4.7 Percentage of Participants |
p-value: 0.638Fisher Exact
Secondary
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
Population: All Randomized participants who are 4 years or older and have both baseline and at least one post-baseline quarterly outcome measure in any quarter. Diaries were only provided to participants 4 years and older.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Quarterly Rate of School Absence Due to Sickle Cell Pain | 11.527 Percentage of Days in a Quarter | Standard Error 1.525 |
| Placebo | Quarterly Rate of School Absence Due to Sickle Cell Pain | 10.255 Percentage of Days in a Quarter | Standard Error 1.466 |
p-value: 0.45995% CI: [-2.109, 4.652]Mixed Models Analysis
Secondary
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)
Population: All randomized participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prasugrel | Time From Randomization to First and Second VOC | Time from Randomization to the First VOC | 90.0 Days |
| Prasugrel | Time From Randomization to First and Second VOC | Time from Randomization to the Second VOC | 338.0 Days |
| Placebo | Time From Randomization to First and Second VOC | Time from Randomization to the First VOC | 87.0 Days |
| Placebo | Time From Randomization to First and Second VOC | Time from Randomization to the Second VOC | 238.0 Days |
Comparison: Time from Randomization to the First VOCp-value: 0.317Log Rank
Comparison: Time from Randomization to the Second VOCp-value: 0.133Log Rank
Secondary
Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke
Time frame: Randomization through 24 Months
Population: No participants had a TIA or ischemic stroke at time of analysis.