A Phase II, Randomized, Placebo-Controlled, Double-Blind (Sponsor Open) Study of GSK1278863, a HIF-Prolyl Hydroxylase Inhibitor, to Reduce Ischemic Events in Patients Undergoing Thoracic Aortic Aneurysm Repair
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Change From Baseline to Peak in CSF Glial Fibrillary Acidic Protein (GFAP) Within 48 Hours Following DTA/TAAA Repair
研究概览
简要总结
This study will test the hypothesis that GSK1278863 will reduce neurologic, renal, and/or cardiac ischemia in patients undergoing elective descending thoracic aorta/thoracoabdominal aortic aneurysm (DTA/TAAA) repair, a population known to be at high risk for ischemic events from their underlying pathology and the surgical complexity required to address their disease. Approximately 160 subjects will be stratified according to intervention type (surgical or endovascular repair, with the latter limited to 50% of the total study population) and randomized in a 1:1 fashion to treatment with GSK1278863 (300 milligrams [loading dose] followed by 100 milligrams [mg]/day x 4 days) or placebo starting prior to planned repair, through postoperative day 3. The duration of participation in this study is expected to be approximately 4 to 8 weeks from screening to follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GSK1278863
Subject will receive GSK1278863 300mg on Day-1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100mg once daily for 4 days starting from Day 0.
干预措施: GSK1278863 (Drug)
Placebo
Subject will receive GSK1278863 matching placebo on Day-1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 matching placebo once daily for 4 days starting from Day 0.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Peak in CSF Glial Fibrillary Acidic Protein (GFAP) Within 48 Hours Following DTA/TAAA Repair
时间窗: Baseline (Day 0) to 48 hours following DTA/TAAA repair
GFAP is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples for the analysis of GFAP was collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF GFAP. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Change From Baseline to Peak in Cerebrospinal Fluid (CSF) S100 Beta Within 48 Hours Following Descending Thoracic Aorta/Thoracoabdominal Aortic Aneurysm (DTA/TAAA) Repair
时间窗: Baseline (Day 0) to 48 hours following DTA/TAAA repair
S100 beta is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF S100 beta. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
次要结局
- PK Parameters in CSF: Tmax of GSK1278863(Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Follow-up (Day 45))
- Number of Participants With Clinical Chemistry Parameters of PCI(Up to post-operative Day 7)
- Number of Participants With Hematology Parameters of PCI(Up to post-operative Day 7)
- Change From Baseline to Peak in CSF Biomarker Neuron-specific Enolase (NSE) Within 48 Hours Following DTA/TAAA Repair(Baseline (Day 0) to 48 hours following DTA/TAAA repair)
- Number of Participants With Neurologic Outcomes Assessed by the National Institutes of Health Stroke Scale (NIHSS)(Surgical Day (Day 0), Post-operative Day 1, 2, 7 and follow-up (Day 45))
- PK Parameters in CSF: Cmax of GSK1278863(Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI)
- Number of Participants With Vital Signs of Potential Clinical Importance (PCI)(Up to Follow-up (Day 45))
- Number of Participants With Abnormal Electrocardiography (ECG) Parameters(Up to Follow-up (Day 45))
- Change From Baseline to Peak in CSF Biomarker Erythropoietin Within 48 Hours Following DTA/TAAA Repair(Baseline (Day 0) to 48 hours following DTA/TAAA repair)
- Number of Participants With Neurologic Outcomes Assessed by the American Spinal Injury Association (ASIA) Lower Extremity Motor Outcome Scale(Surgical Day (Day 0), Post-operative Day 1, 2, 7 and follow-up (Day 45))
- Assessment in AUC for Markers of Ischemic Organ Injury Including Tropinin Within 48 Hours(Baseline (Day 0) and 8 to 48 hours following DTA/TAAA repair)
- PK Parameters in CSF: AUC(0-t) of GSK1278863(Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI)
- PK Parameters in Blood: Maximum Observed Concentration (Cmax) of GSK1278863(Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3)
- Change From Baseline in Area Under Curve (AUC) for CSF S100 Beta to 48 Hours(Baseline(Day 0) to 48 hours following DTA/TAAA repair)
- Change From Baseline in AUC for CSF GFAP to 48 Hours(Baseline(Day 0) to 48 hours following DTA/TAAA repair)
- Change From Baseline to Peak in CSF Biomarker Lactate Dehydrogenase Within 48 Hours Following DTA/TAAA Repair(Baseline (Day 0) to 48 hours following DTA/TAAA repair)
- Change From Baseline to Peak in CSF Biomarker Tau Protein Within 48 Hours Following DTA/TAAA Repair(Baseline (Day 0) to 48 hours following DTA/TAAA repair)
- Number of Participants With Clinical Composite of All Cause Mortality, Stroke, Spinal Infarction, MI, Need for Dialysis/Sustained Doubling of Serum Creatinine(Up to Follow-up (Day 45))
- Pharmacokinetic (PK) Parameters in Blood: AUC(0-t) of GSK1278863(Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3)
- Number of Participants With Neurologic Outcomes Assessed by Modified Rankin Scale (mRS)(Post-operative Day 7 and follow-up (Day 45))
- PK Parameters in Blood: Time of Occurrence of Cmax (Tmax) of GSK1278863(Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3)
- Number of Participants With Composite Index of All Cause Mortality and Disability (NIHSS>5/ASIA<40)(Up to Follow-up (Day 45))