Study of GSK1278863 to Reduce Ischemic Events in Patients Undergoing Thoracic Aortic Aneurysm Repair
Surgical Procedures
Bottom Line
View on ClinicalTrials.gov: NCT01920594 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK1278863 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Peak in Cerebrospinal Fluid (CSF) S100 Beta Within 48 Hours Following Descending Thoracic Aorta/Thoracoabdominal Aortic Aneurysm (DTA/TAAA) Repair |
2748.19; 566.78 | 0.0820 |
| PRIMARY Change From Baseline to Peak in CSF Glial Fibrillary Acidic Protein (GFAP) Within 48 Hours Following DTA/TAAA Repair |
1078.61; 283.03 | 0.1997 |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
26; 23; 20; 14 | — |
| SECONDARY Number of Participants With Vital Signs of Potential Clinical Importance (PCI) |
2; 1; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiography (ECG) Parameters |
18; 18; 18; 17; 17; 16 | — |
| SECONDARY Number of Participants With Clinical Chemistry Parameters of PCI |
19; 18 | — |
| SECONDARY Number of Participants With Hematology Parameters of PCI |
25; 16 | — |
| SECONDARY Change From Baseline in Area Under Curve (AUC) for CSF S100 Beta to 48 Hours |
17263.25; 9758.27 | 0.1530 |
| SECONDARY Change From Baseline in AUC for CSF GFAP to 48 Hours |
182.35; 58.32 | 0.1377 |
| SECONDARY Change From Baseline to Peak in CSF Biomarker Erythropoietin Within 48 Hours Following DTA/TAAA Repair |
1.34; 0.61 | <.0001 sig |
| SECONDARY Change From Baseline to Peak in CSF Biomarker Lactate Dehydrogenase Within 48 Hours Following DTA/TAAA Repair |
1.82; 1.28 | 0.2404 |
| SECONDARY Change From Baseline to Peak in CSF Biomarker Tau Protein Within 48 Hours Following DTA/TAAA Repair |
1729.25; 751.21 | 0.0526 |
| SECONDARY Change From Baseline to Peak in CSF Biomarker Neuron-specific Enolase (NSE) Within 48 Hours Following DTA/TAAA Repair |
9.31; 5.65 | 0.0893 |
| SECONDARY Number of Participants With Neurologic Outcomes Assessed by the National Institutes of Health Stroke Scale (NIHSS) |
27; 23; 0; 3; 11; 14 | — |
| SECONDARY Number of Participants With Neurologic Outcomes Assessed by Modified Rankin Scale (mRS) |
9; 11; 1; 8; 10; 5 | — |
| SECONDARY Number of Participants With Neurologic Outcomes Assessed by the American Spinal Injury Association (ASIA) Lower Extremity Motor Outcome Scale |
26; 26; 1; 0; 15; 19 | — |
| SECONDARY Number of Participants With Clinical Composite of All Cause Mortality, Stroke, Spinal Infarction, MI, Need for Dialysis/Sustained Doubling of Serum Creatinine |
13; 10; 1; 0; 6; 4 | — |
| SECONDARY Assessment in AUC for Markers of Ischemic Organ Injury Including Tropinin Within 48 Hours |
13.29; 7.23; 3.14; 4.19 | 0.5012 |
| SECONDARY Number of Participants With Composite Index of All Cause Mortality and Disability (NIHSS>5/ASIA<40) |
4; 1; 4; 2; 6; 2 | — |
| SECONDARY Pharmacokinetic (PK) Parameters in Blood: AUC(0-t) of GSK1278863 |
3591.449; 2858.165; 3710.790 | — |
| SECONDARY PK Parameters in CSF: AUC(0-t) of GSK1278863 |
37.340 | — |
| SECONDARY PK Parameters in Blood: Maximum Observed Concentration (Cmax) of GSK1278863 |
705.701; 358.518; 779.801 | — |
| SECONDARY PK Parameters in CSF: Cmax of GSK1278863 |
2.364 | — |
| SECONDARY PK Parameters in Blood: Time of Occurrence of Cmax (Tmax) of GSK1278863 |
1.725; 3.017; 3.017 | — |
| SECONDARY PK Parameters in CSF: Tmax of GSK1278863 |
15.326 | — |
Summary
Eligibility Criteria
Inclusion Criteria
- Adults >= 18 years of age who require the following types of descending thoracic aorta or thoracoabdominal aorta repair for atherosclerotic aneurysm or chronic dissection (de novo Type B or residual Type B [following Type A repair]) via open surgery or endovascular stenting (TEVAR) as per their treating surgeon
- Open surgery:
Extent I TAAA (+/-distal arch) if it extends to or beyond renal ostia. Extent II TAAA (+/-distal arch). Extent III TAAA (defined as proximal extent or anastamosis superior to inferior pulmonary vein).
Extent IV TAAA only with a prior TEVAR or if it is a redo procedure (in this setting a "redo" is a prior abdominal aortic aneurysm (AAA) open or endovascular aortic repair (EVAR), with either proximal suture line disruption or mesenteric segment aneurysm recurrence requiring redo Extent IV reconstruction).
DTA repair with one of the following: Safi extent C coverage. Subclavian to diaphragm disease extent. >75% of total DTA length.
-TEVAR with one of the following: Full DTA coverage with previous abdominal EVAR or open AAA. Full DTA coverage including Zone 2 to celiac (i.e., distal arch plus full coverage DTA).
Full DTA coverage with celiac artery coverage with or without left subclavian artery coverage (Zone 2 or Zone 3 proximal landing), or full DTA (either Zone 2 or Zone 3) with extension distal to celiac with visceral debranching (e.g., the abdominal hybrid Extent 2 TAAA).
Note: Zone 2 is defined as between the left carotid through coverage of the left subclavian artery and Zone 3 is defined as the first 3cm distal to the left subclavian (e.g., between left subclavian and ligamentum [isthmus]).
- Completed any staging or bypass procedure that precedes the aortic repair at least 48 hours prior to the repair.
- Expect placement of a lumbar CSF catheter during the procedure with plans to maintain it for at least 48 hours per the treating physician.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- A female subject is eligible to participate if she is of:
Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli international unit /mililiter (mL) and estradiol 1 or modified Rankin Scale > 1.
- The subject has a history of myocardial infarction, stroke, or spinal infarct within the past 3 months.
- The subject has active ulcer disease or recent gastrointestinal bleeding within the past 6 months.
- The subject has a history of deep venous thrombosis or pulmonary embolism in the past 12 months.
- The subject has been treated for a malignancy (excluding non-melanomatous skin cancers) within the past 12 months and is not confirmed to be disease free.
- The subject has had treatment for retinal neovascularization (e.g., diabetic proliferative retinopathy or age related macular degeneration) within 3 months of randomization.
- The subject is currently receiving dialysis.
- The subject is currently receiving or expected to require treatment (within the study period) with erythropoiesis medication such as epoetin alfa (Procrit, Epogen), or darbepoetin alfa (Aranesp).
- The subject has any of the following at screening:
Hemoglobin >15.5 gram (g)/decilitre (dL) (male subjects or post-menopausal females) Hemoglobin >14.5 g/dL (pre-menopausal female subjects) Single QTc >=480 millisecond (msec); or QTc >=500 msec in subjects with bundle branch block (these criteria do not apply to subjects with predominately paced rhythms) Aspartate aminotransferase and alanine aminotransferase >=2xupper limit of normal (ULN); alkaline phosphatase and bilirubin >=1.5xULN (isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 14 drinks for males or >7 drinks for f
Data sourced from ClinicalTrials.gov (NCT01920594). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.