Study on Ketorolac for Improving Outcomes and Prognosis in Patients With Stanford Type A Aortic Dissection
- Conditions
- Aortic DissectionInflammation
- Interventions
- Drug: 0.9 % saline
- Registration Number
- NCT06968806
- Lead Sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 360
- Patients with Stanford Type A aortic dissection confirmed by imaging and scheduled for emergency surgery.
Aged between 18 and 65 years.
Signed informed consent.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ketorolac Group 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. Placebo Group 0.9 % saline 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
- Primary Outcome Measures
Name Time Method Composite Endpoint: Mortality, Malperfusion Syndrome, Permanent Organ Dysfunction, Unplanned Cardiac Reoperation, and Prolonged Hospitalization 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.
- Secondary Outcome Measures
Name Time Method Survival rate the 1-year follow-up Survival rate refers to the percentage of patients who remain alive for a specified period after diagnosis or treatment of a disease. It is a key metric in evaluating treatment efficacy, disease prognosis, and healthcare outcomes.
NYHA he 1-year follow-up NYHA classification is a widely used system to categorize the severity of heart failure symptoms based on a patient's physical limitations. It helps clinicians assess disease progression, guide treatment decisions, and predict outcomes.
Creatinine Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Creatinine is a waste product generated from the breakdown of creatine phosphate in muscles. It is filtered by the kidneys and excreted in urine, making it a key marker for kidney function.
Complete Blood Count (CBC) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 A Complete Blood Count (CBC) is a common blood test that evaluates overall health and detects a wide range of disorders, including infections, anemia, and leukemia. It measures several components and features of the blood
Creatine Kinase (CK) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Creatine Kinase (CK), also known as Creatine Phosphokinase (CPK), is an enzyme that plays a critical role in cellular energy metabolism. It catalyzes the conversion of creatine + ATP ↔ phosphocreatine + ADP, providing rapid energy for muscle contraction.
erythrocyte sedimentation rate (ESR) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 erythrocyte sedimentation rate (ESR), an indicator of systemic inflammation that reflects the rate at which red blood cells settle in a vertical tube over a specified period. Elevated ESR levels may suggest ongoing inflammatory responses, infection, or tissue injury
The perioperative use of opioids perioperative The perioperative use of opioids such as fentanyl and remifentanil is also assessed
C-reactive protein (CRP) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 C-reactive protein (CRP), an acute-phase protein synthesized by the liver that rises rapidly in response to infection, inflammation, or tissue injury. CRP serves as a sensitive biomarker of systemic inflammatory response and will be used to assess the perioperative inflammatory status in patients with Stanford Type A aortic dissection.
interleukin-6 (IL-6) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 interleukin-6 (IL-6), a pro-inflammatory cytokine produced by various cells in response to tissue injury, infection, or stress. IL-6 plays a key role in the acute-phase inflammatory response and is closely associated with the severity of systemic inflammation.
Procalcitonin (PCT) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Procalcitonin (PCT) is a protein precursor of the hormone calcitonin, which is involved in calcium metabolism. Normally, PCT is produced in the thyroid C cells and is present in very low levels in the blood. However, during severe bacterial infections, levels rise significantly, making it a useful biomarker for diagnosing and monitoring bacterial infections, sepsis, and guiding antibiotic therapy.
Prothrombin Time (PT) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Prothrombin Time (PT) is a blood test that measures how long it takes for plasma to clot after adding thromboplastin (a reagent that activates the extrinsic pathway of coagulation). It evaluates the function of the extrinsic pathway (Factor VII) and common pathway (Factors X, V, II, and fibrinogen).
Activated Partial Thromboplastin Time (aPTT) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Activated Partial Thromboplastin Time (aPTT) is a fundamental coagulation test that measures the time required for plasma to clot after activation of the intrinsic pathway. This test evaluates the functionality of all coagulation factors except Factor VII and XIII.
Platelet function Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Platelet function refers to the ability of platelets to participate in hemostasis through adhesion, activation, aggregation, and procoagulant activity. Proper platelet function is essential for primary hemostasis and vascular repair.
Alanine Aminotransferase (ALT) Preoperative and postoperative assessments on days 1, 3, 5, 7, 30, and 90 Alanine Aminotransferase (ALT), also known as serum glutamate-pyruvate transaminase (SGPT), is a liver enzyme primarily found in hepatocytes. It plays a key role in amino acid metabolism by catalyzing the transfer of an amino group from alanine to α-ketoglutarate, producing pyruvate and glutamate.
Cardiopulmonary Bypass (CPB) Time Intraoperative Cardiopulmonary Bypass (CPB) Time refers to the duration (in minutes) during which a patient's circulatory and respiratory functions are temporarily supported by a heart-lung machine during cardiac surgery. This allows surgeons to operate on a still, bloodless heart.
Total Surgical Duration Intraoperative Total Surgical Duration refers to the entire time from skin incision to wound closure during a surgical procedure. It is a critical metric in perioperative medicine, influencing patient outcomes, resource utilization, and surgical team performance.
Postoperative drainage Perioperative/Periprocedural Postoperative drainage refers to the fluid collected from surgical sites via drains, providing critical information about healing and complications. Monitoring its volume and characteristics helps guide clinical decisions.
Transfusion requirements Perioperative/Periprocedural Transfusion requirements refer to the amount and type of blood products needed during or after surgery to maintain adequate oxygenation, hemostasis, and hemodynamic stability. The volume transfused depends on blood loss, preoperative anemia, and patient physiology.
Postoperative sternal infection (PSI) Perioperative/Periprocedural Postoperative sternal infection (PSI) refers to surgical site infections involving the sternum after cardiac or thoracic surgery, particularly following median sternotomy. These infections range from superficial wound complications to life-threatening mediastinitis.
Number of Participants with breakthrough pain Perioperative/Periprocedural Incidence: 20-40% of surgical patients experience inadequately controlled pain requiring rescue analgesia.
Risk Factors:
Major surgery (e.g., orthopedic, abdominal)
Preoperative opioid use
Younger ageNumber of Participants with nausea Perioperative/Periprocedural Nausea is an unpleasant, subjective sensation of impending vomiting, often accompanied by autonomic symptoms like pallor, sweating, and increased salivation. As a common postoperative complication, it represents a significant challenge in perioperative care.
Number of Participants with vomiting Perioperative/Periprocedural Vomiting (emesis) is the forceful expulsion of gastric contents through the mouth resulting from coordinated contractions of the abdominal, thoracic, and gastrointestinal musculature. As a protective reflex mediated by the brainstem, it serves to eliminate harmful substances but becomes clinically significant when occurring postoperatively or pathologically.
Number of Participants with gastrointestinal discomfort Perioperative/Periprocedural Gastrointestinal (GI) discomfort refers to a spectrum of subjective abdominal symptoms occurring postoperatively, distinct from nausea/vomiting. This nonspecific symptom complex affects 15-40% of surgical patients and significantly impacts recovery trajectories.
aortic tissue density the 1-year follow-up imaging-based radiomics and biomechanical analyses from CTA and other modalities are used to evaluate aortic tissue density
aortic tissue strength the 1-year follow-up maging-based radiomics and biomechanical analyses from CTA and other modalities are used to evaluate aortic tissue strength
abnormal blood flow the 1-year follow-up imaging-based radiomics and biomechanical analyses from CTA and other modalities are used to evaluate abnormal blood flow
Trial Locations
- Locations (1)
Nanjing Drum Tower Hospital
🇨🇳Nanjing, Jiangsu, China