Aortic Dissection, Inflammation
Conditions
Keywords
Ketorolac, Stanford type A aortic dissection, RCT
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.
Interventions
DRUGKetorolac
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.
DRUG0.9 % saline
0.9% saline
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Guangdong Provincial People's Hospital
Huai'an First People's Hospital
Shandong Provincial Hospital
First Affiliated Hospital of Harbin Medical University
The Second Affiliated Hospital of Harbin Medical University
The First Affiliated Hospital of Shihezi University
Xinhua Hospital of Ili Kazak Autonomous Prefecture
Henan Provincial Chest Hospital
First Affiliated Hospital of Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
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 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. 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary endpoints | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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 age |
| Number 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 |
| 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. |
| Postoperative recovery and complications | he 1-year follow-up | ICU length of stay, duration of mechanical ventilation, total hospital stay, incidence of pneumonia, permanent dialysis, tracheostomy, neurological dysfunction, secondary debridement, cardiac arrest, mechanical circulatory support, or unplanned cardiac reoperation (excluding those due to bleeding), postoperative cardiac arrest, multiple organ dysfunction, and mechanical ventilation duration exceeding 72 hours. |
Countries
China
Contacts
CONTACTTuo Pan, MD
CONTACTDongjin Wang, MD
STUDY_DIRECTORTuo Pan, MD
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
STUDY_CHAIRDongJin Wang, MD
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
PRINCIPAL_INVESTIGATORDongJin Wang, MD
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Outcome results
None listed