Study on Ketorolac for Improving Outcomes and Prognosis in Patients With Stanford Type A Aortic Dissection

Official title

Study on Ketorolac for Improving Outcomes and Prognosis in Patients With Stanford Type A Aortic Dissection -A Single-Center, Randomized, Double-Blind, Controlled Clinical Trial

Overview

This multicenter, randomized, double-blind, placebo-controlled trial evaluates the efficacy and safety of ketorolac in 360 patients with Stanford Type A aortic dissection, conducted between 2025 and 2027. Participants will receive either ketorolac (60 mg intramuscularly \[IM\] preoperatively and 30 mg twice daily \[BID\] 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 360 eligible patients with Stanford Type A aortic dissection between March 2025 and December 2027. Participants will be equally randomized to receive either ketorolac (intervention group: 60 mg intramuscular \[IM\] preoperatively followed by 30 mg twice daily \[BID\] 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.

Interventions

• Drug Ketorolac
  patients in the experimental group will receive ketorolac treatment for Stanford Type A aortic dissection, consisting of a 60mg intramuscular injection preoperatively followed by 30mg twice daily for two days postoperatively, while maintaining standard baseline therapies including analgesia, blood pressure control, and subsequent cardiovascular surgical management.
• Drug 0.9 % saline
  0.9% saline

Primary outcome measures

• 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.]

Secondary outcome measures (12)

• erythrocyte sedimentation rate (ESR) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• The perioperative use of opioids [Time frame: perioperative]
• C-reactive protein (CRP) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• interleukin-6 (IL-6) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Complete Blood Count (CBC) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Procalcitonin (PCT) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Prothrombin Time (PT) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Activated Partial Thromboplastin Time (aPTT) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Platelet function [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Alanine Aminotransferase (ALT) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Creatinine [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]
• Creatine Kinase (CK) [Time frame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90]

Eligibility criteria

Inclusion criteria

• Patients with Stanford Type A aortic dissection confirmed by imaging and scheduled for emergency surgery.

Aged between 18 and 65 years.

Signed informed consent.

Exclusion criteria

• Patients who are unable to eat independently or require prolonged fasting.

History of malignant tumors.

Body weight <50 kg.

Traumatic aortic dissection.

Patients with Marfan syndrome.

Unstable vital signs requiring preoperative mechanical support or resuscitation (e.g., IABP \[Intra-Aortic Balloon Pump\], ECMO \[Extracorporeal Membrane Oxygenation\], LVAD \[Left Ventricular Assist Device\])

Patients requiring preoperative endotracheal intubation.

Consciousness impairment, central nervous system dysfunction, or evidence of cerebral malperfusion syndrome upon admission.

Preoperative hematemesis, melena, fresh blood in stool, or symptoms of bowel dilation.

Clear evidence of limb malperfusion before surgery.

Presence of organ malperfusion syndrome.

Patients requiring interventional procedures to relieve organ malperfusion before surgery.

History of gastrointestinal ulcers or chronic gastrointestinal inflammatory diseases.

History of dialysis or renal insufficiency before admission.

History of liver disease.

Allergy to ketorolac tromethamine, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs).

Chronic inflammatory diseases, autoimmune diseases, or long-term use of steroids or NSAIDs for other reasons.

Absence of cerebral perfusion during deep hypothermic circulatory arrest.

History of major surgery or acute myocardial infarction within 90 days.

History of cardiac or major vascular surgery.

Pregnant or lactating women.

Patients who refuse to participate in this clinical trial or decline to sign the informed consent form.

Any other conditions deemed unsuitable for participation by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Nanjing Drum Tower Hospital — Nanjing

Identifiers

NCT: NCT06968806 · 2025 -0039-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗