Clinical trial NCT06968806: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Aortic Dissection
Inflammation
Keywords: Inflammation
Aortic Dissection
Ketorolac
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
Collaborators: name: Guangdong Provincial People's Hospital
name: Huai'an First People's Hospital
name: Shandong Provincial Hospital
name: First Affiliated Hospital of Harbin Medical University
name: The Second Affiliated Hospital of Harbin Medical University
name: THE FIRST AFFILIATED HOSPITAL OF SHIHEZI UNIVERSITY
name: Xinhua Hospital of Ili Kazak Autonomous Prefecture
First posted: 2025-05-13
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After enrollment, 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. The control group will receive identical placebo treatment (0.9% 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Composite Endpoint: Mortality, Malperfusion Syndrome, Permanent Organ Dysfunction, Unplanned Cardiac Reoperation, and Prolonged Hospitalization
timeFrame: Continuous intervention for 3 days after admission, with a 1-year follow-up.
Secondary outcomes:
measure: erythrocyte sedimentation rate (ESR)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: The perioperative use of opioids
timeFrame: perioperative
measure: C-reactive protein (CRP)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: interleukin-6 (IL-6)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Complete Blood Count (CBC)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Procalcitonin (PCT)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Prothrombin Time (PT)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Activated Partial Thromboplastin Time (aPTT)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Platelet function
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Alanine Aminotransferase (ALT)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Creatinine
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Creatine Kinase (CK)
timeFrame: Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90
measure: Cardiopulmonary Bypass (CPB) Time
timeFrame: Intraoperative
measure: Total Surgical Duration
timeFrame: Intraoperative
measure: Postoperative drainage
timeFrame: Perioperative/Periprocedural
measure: Transfusion requirements
timeFrame: Perioperative/Periprocedural
measure: Postoperative sternal infection (PSI)
timeFrame: Perioperative/Periprocedural
measure: Number of Participants with breakthrough pain
timeFrame: Perioperative/Periprocedural
measure: Number of Participants with nausea
timeFrame: Perioperative/Periprocedural
measure: Number of Participants with vomiting
timeFrame: Perioperative/Periprocedural
measure: Number of Participants with gastrointestinal discomfort
timeFrame: Perioperative/Periprocedural
measure: aortic tissue density
timeFrame: the 1-year follow-up
measure: aortic tissue strength
timeFrame: the 1-year follow-up
measure: abnormal blood flow
timeFrame: the 1-year follow-up
measure: Survival rate
timeFrame: the 1-year follow-up
measure: NYHA
timeFrame: he 1-year follow-up
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Tuo Pan, MD
role: STUDY_DIRECTOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: DongJin Wang, MD
role: STUDY_CHAIR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: DongJin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: