Efficacy and Safety of Ketorolac in Improving Prognosis of Stanford Type A Aortic Dissection: a Multicenter, Randomised, Double-blind, Controlled Clinical Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Enrollment
- 1,346
- Locations
- 1
- Primary Endpoint
- Composite Endpoint: Mortality, Malperfusion Syndrome, Permanent Organ Dysfunction, Unplanned Cardiac Reoperation, and Prolonged Hospitalization
Study Overview
Brief Summary
This multicenter, randomized, double-blind, placebo-controlled trial evaluates the efficacy and safety of ketorolac in 1,346 patients with Stanford Type A aortic dissection, conducted between 2025 and 2028. Participants will receive either ketorolac (60 mg intramuscularly [IM] within 6 hours before surgery and 30 mg im twice daily（at 6:00 AM and 6:00 PM, respectively for two days postoperatively or placebo in addition to standard care. Study outcomes include composite clinical endpoints, postoperative complications, and adverse events, which will be assessed through clinical evaluations, laboratory testing, and imaging studies at predefined intervals up to 90 days. The objective of this trial is to determine whether perioperative administration of ketorolac improves clinical outcomes in this patient population.
Detailed Description
This multicenter, randomized, double-blind, controlled clinical trial will enroll 1,346 eligible patients with Stanford Type A aortic dissection between October 2025 and December 2028. Participants will be equally randomized to receive either ketorolac (intervention group: 60 mg intramuscularly [IM] within 6 hours before surgery and 30 mg im twice daily（at 6:00 AM and 6:00 PM, respectively for two days postoperatively) or matching placebo (control group), with both groups receiving standard perioperative care including analgesia, blood pressure control, and surgical treatment. Comprehensive data collection will include demographic characteristics, clinical parameters, laboratory tests (complete blood count [CBC], biochemistry, coagulation profile, cardiac enzymes, procalcitonin, cultures), and imaging studies (radiomics, biomechanics, chest X-ray, ultrasound, computed tomography [CT], magnetic resonance imaging [MRI]) at multiple timepoints from admission through 90-day follow-up. The primary outcomes will focus on evaluating the efficacy and safety of ketorolac through analysis of composite endpoint events, complication rates, and adverse reactions, with immediate study discontinuation and reporting for any treatment-related adverse events. All treatment protocols will maintain identical administration schedules and formulations between groups, with the exception of the active drug versus placebo.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The criteria for inclusion are: (1) Imaging diagnosis of ATAAD and planning for emergency surgery; (2) Age between 18 and 65 years; (3) Signed informed consent; (4) First median sternotomy; (5) Duration from symptom onset to surgery less than or equal to 7 days; (6) Preoperative data are complete; (7) Glasgow Coma Scale (GCS) score greater than or equal to 15, with no new focal neurological deficits.
Exclusion Criteria
- •The criteria for exclusion include: (1) Extended periods of fasting or inability to feed oneself; (2) A history of cancer; (3) Weight below 50 kg; (4) Traumatic dissections of the aorta; (5) Individuals diagnosed with Marfan syndrome; (6) Preoperative vital sign instability necessitating mechanical assistance or resuscitation ; (7) The duration of preoperative tracheal intubation exceeds 3 days. (8) Disorders of consciousness, central nervous system issues, or signs of inadequate brain perfusion after admission; (9) Preoperative gastrointestinal involvement and intestinal dilation； (10) Clear signs of inadequate limb perfusion before the procedure; (11) Presence of organ perfusion insufficiency syndrome; (12) Patients needing preliminary surgical intervention to address organ perfusion issues; (13) A history of gastrointestinal ulcers or chronic inflammation of the gastrointestinal tract;;(14) Preoperative hepatic and renal dysfunction;(15) Allergies to ketorolac tromethamine, aspirin, or other NSAIDs; (16) Chronic inflammatory or autoimmune conditions requiring long-term hormone or NSAID use; (17) Absence of brain perfusion during deep hypothermic circulatory arrest; (18) A history of grade IV surgery or acute myocardial infarction within the last 90 days; (19) Previous cardiac or major vascular surgeries; (20) Pregnant or breastfeeding women; (21) Cardiopulmonary bypass (CPB) lasting over 4 hours, deep hypothermic circulatory arrest (DHCA) exceeding 40 minutes, or total surgical time over 10 hours; (22) Any other conditions considered inappropriate for participation by the researchers.
Arms & Interventions
Placebo Group
The control group will receive identical placebo treatment (normal saline) with the same dosage regimen, formulation, and timing of administration as the experimental group, while also continuing all standard baseline treatments and surgical interventions without modification. Both groups will follow identical protocols except for the active drug versus placebo
Intervention: 0.9 % saline (Drug)
Ketorolac Group
patients in the experimental group will receive ketorolac treatment for Stanford Type A aortic dissection, consisting of a 60mg intramuscular injection within 6 hours before surgery followed by 30mg im twice daily(at 6:00 AM and 6:00 PM, respectively )for two days postoperatively, while maintaining standard baseline therapies including analgesia, blood pressure control, and subsequent cardiovascular surgical management.
Intervention: Ketorolac (Drug)
Outcomes
Primary Outcomes
Composite Endpoint: Mortality, Malperfusion Syndrome, Permanent Organ Dysfunction, Unplanned Cardiac Reoperation, and Prolonged Hospitalization
Time Frame: Continuous intervention for 3 days after admission, with a 1-year follow-up.
The composite endpoint includes death (the worst outcome); malperfusion syndrome (including myocardial ischemia, stroke, lower limb paralysis, acute abdominal syndrome, renal failure requiring temporary dialysis, or symptoms and signs of limb ischemia); permanent dialysis, tracheostomy, or neurological deficits at discharge; postoperative mechanical circulatory support or unplanned cardiac reoperation (excluding reoperation for bleeding); postoperative cardiac arrest, multiple organ failure, or mechanical ventilation support for more than 72 hours; and postoperative hospital stay of 91 days or longer.
Primary endpoints
Time Frame: Continuous intervention for 3 days after admission, with a 1-year follow-up.
In-hospital mortality and the occurrence of organ malperfusion syndrome (including myocardial ischemia, stroke, lower limb paralysis, acute abdominal pain, renal failure requiring temporary dialysis, or limb ischemia) during the hospitalization.
Secondary Outcomes
- Creatinine(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Creatine Kinase (CK)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- erythrocyte sedimentation rate (ESR)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- The perioperative use of opioids(perioperative)
- C-reactive protein (CRP)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- interleukin-6 (IL-6)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Complete Blood Count (CBC)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Procalcitonin (PCT)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Prothrombin Time (PT)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Activated Partial Thromboplastin Time (aPTT)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Platelet function(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Alanine Aminotransferase (ALT)(Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90)
- Cardiopulmonary Bypass (CPB) Time(Intraoperative)
- Total Surgical Duration(Intraoperative)
- Postoperative drainage(Perioperative/Periprocedural)
- Transfusion requirements(Perioperative/Periprocedural)
- Postoperative sternal infection (PSI)(Perioperative/Periprocedural)
- Number of Participants with breakthrough pain(Perioperative/Periprocedural)
- Number of Participants with nausea(Perioperative/Periprocedural)
- Number of Participants with vomiting(Perioperative/Periprocedural)
- Number of Participants with gastrointestinal discomfort(Perioperative/Periprocedural)
- aortic tissue density(the 1-year follow-up)
- aortic tissue strength(the 1-year follow-up)
- abnormal blood flow(the 1-year follow-up)
- Survival rate(the 1-year follow-up)
- NYHA(he 1-year follow-up)
- Postoperative recovery and complications(he 1-year follow-up)