Remote Ischemic Preconditioning for Aute Type A Aortic Dissection Surgery

Evaluation of the Organ-Protective Effects of Remote Ischemic Preconditioning in Patients Undergoing Surgery for Acute Type A Aortic Dissection: A Multicenter, Prospective, Double-Blind, Randomized Controlled Trial

The goal of this clinical trial is to learn if a technique called remote ischemic preconditioning (RIPC) helps protect organs during emergency surgery for acute type A aortic dissection (ATAAD). The main questions it aims to answer are:

Does RIPC reduce the risk of major complications after surgery, such as heart, brain, or kidney problems?

Is RIPC safe to use during emergency ATAAD surgery?

Researchers will compare the RIPC group to a control group (who will receive a placebo) to see if RIPC can reduce complications after surgery.

Participants will:

Receive either RIPC or a sham intervention during their surgery.

Be monitored for up to 30 days after surgery for complications.

Have follow-up visits at 3 months, 1 year, and then yearly for up to 5 years to track their recovery.

Study Overview

• Status: Recruiting
• Conditions: Aortic Dissection Type A
• Intervention / Treatment: Procedure: Remote ischemic preconditioning (RIPC)

Detailed Description

Study Design and Rationale

This study is a multicenter, prospective, double-blind, randomized, sham-controlled clinical trial designed to evaluate the organ-protective efficacy and safety of remote ischemic preconditioning (RIPC) in patients undergoing emergency surgery for acute type A aortic dissection (ATAAD).

Primary Objective

The primary objective of this study is to determine whether RIPC reduces the incidence of the primary composite endpoint of major adverse outcomes occurring from the time of surgery until hospital discharge (or up to 30 days postoperatively if hospitalization exceeds 30 days). This composite endpoint includes perioperative all-cause mortality and severe complications requiring invasive intervention or resulting in organ failure.

Key Interventions and Methodology Intervention Group

After induction of general anesthesia, patients in the intervention group receive the RIPC procedure. On the non-arterial cannulation side, alternating RIPC cycles are applied to both the upper arm and thigh, for a total of four cycles. The protocol begins with the upper arm cuff.

Each cycle consists of 5 minutes of cuff inflation (baseline pressure of 200 mm Hg; or at least 15 mm Hg above systolic pressure if systolic pressure exceeds 185 mm Hg), followed by 5 minutes of cuff deflation to allow reperfusion. The first cycle of the thigh cuff is initiated after completion of the first inflation cycle of the upper arm cuff.

Control Group

Patients in the control group undergo a sham procedure identical in timing and application sites to the RIPC intervention. However, the cuff is inflated to a low, non-ischemic pressure of 20 mm Hg for 5 minutes, followed by 5 minutes of deflation in each cycle.

Blinding

This study employs a double-blind design. Study participants, surgical teams, postoperative care providers, outcome assessors, and data analysts/statisticians are all blinded to treatment allocation. Only an independent researcher, who does not participate in subsequent patient assessment or data collection, is unblinded in order to perform the assigned intervention.

Standardization

All surgical procedures and perioperative care are conducted in accordance with standardized protocols at each participating center.

Study Endpoints Primary Endpoint

The incidence of the primary composite endpoint of major adverse outcomes from surgery until hospital discharge (or up to 30 days postoperatively).

Secondary Endpoints

Secondary endpoints include the incidence of each individual component of the primary composite endpoint at 30 days, 90 days, and 12 months postoperatively; the maximum SOFA-2 score within the first 3 postoperative days; surgery- and cardiopulmonary bypass-related times; duration of mechanical ventilation; lengths of intensive care unit (ICU) and hospital stay; postoperative all-cause mortality; and the rate of unplanned rehospitalization.

Quality Assurance and Data Management Site Selection and Training

Participating centers are required to have substantial experience in emergency ATAAD surgery. All investigators undergo centralized training on the study protocol and Standard Operating Procedures (SOPs), with a focus on the standardized RIPC procedure and data collection.

Clinical Monitoring

Clinical Research Associates (CRAs) conduct periodic on-site monitoring visits to ensure adherence to the study protocol and to verify consistency between data entered in the electronic Case Report Forms (eCRFs) and source documents.

Statistical Analysis

The primary analysis will be conducted in the intention-to-treat (ITT) population. Continuous variables will be compared using appropriate parametric or non-parametric tests, and categorical variables will be compared using the chi-square test or Fisher's exact test, as appropriate.

Sample Size Justification

Based on previously reported literature indicating an incidence of major adverse outcomes of approximately 25.8% after ATAAD surgery, and assuming an anticipated relative risk reduction of 26.5% with RIPC, sample size calculations using a two-sided alpha level of 0.05 and 80% statistical power determined that 589 evaluable patients are required per group. Allowing for an estimated dropout rate of 10%, the final target enrollment for this study is 1,296 patients.

Interim Analysis and Data Safety Monitoring

An independent Data and Safety Monitoring Board (DSMB) will oversee participant safety throughout the study and periodically review aggregated safety data.

A pre-specified blinded sample size re-estimation will be performed when approximately 600 participants have completed assessment of the primary endpoint. This analysis will be based on the pooled event rate and observed dropout rate only, without unblinding treatment allocation or conducting between-group efficacy comparisons. Therefore, the interim analysis will not affect the overall type I error rate.

• Study Type: Interventional
• Enrollment (Estimated): 1296
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liang-wan Chen, M.D Ph.D; Phone Number: +8613358255333; Email: chenliangwan@fjmu.edu.cn
• Study Contact Backup: Name: Xin-fan Lin, M.D; Phone Number: +8617850019550; Email: lxf1885@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
      • Contact: Liang-wan Chen; Phone Number: +8613358255333; Email: chenliangwan@fjmu.edu.cn
    • Xiamen, Fujian, China
      • Not yet recruiting
      • Xiamen Cardiovascular Hospital, Xiamen University
      • Contact: Zhi Lin; Email: proflinz@xmu.edu.cn
  • Liaoning
    • Dalian, Liaoning, China
      • Not yet recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Xiao-ming Bian; Email: bxiaoming@dmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years, with no restriction on sex;
2. Diagnosis of acute Type A aortic dissection requiring emergency surgery (symptom onset <14 days);
3. Ability to understand the study objectives, voluntary provision of written informed consent by the patient or a legally authorized representative, and willingness to comply with follow-up.

Exclusion Criteria:

1. Traumatic or iatrogenic aortic dissection;
2. Previous open cardiac or thoracic aortic surgery;
3. Severe preoperative dysfunction of vital organs, such as persistent deep coma, abdominal compartment syndrome, or circulatory failure;
4. Severe comorbidities, including myocardial infarction within the past 7 days, stroke within the past 2 months; end-stage renal disease (eGFR <30 ml/min/1.73 m²); end-stage liver disease (total bilirubin >342 μmol/L or INR >2.0);
5. Evidence of ischemia in the limb planned for intervention, such as decreased skin temperature, pain, pallor, with or without sensory disturbance, paralysis, or diminished/absent pulses; or severe deformity or prior arteriovenous surgery at the intervention site;
6. Peripheral arterial disease involving the limbs, Raynaud phenomenon, active phlebitis, or a history of deep vein thrombosis of the lower extremities;
7. Current use of sulfonylurea oral hypoglycemic agents or nicorandil;
8. Life expectancy <1 year (e.g., advanced malignancy);
9. Participation in another clinical trial without having reached its primary endpoint;
10. Pregnancy or lactation; immunodeficiency (e.g., HIV positivity, history of organ transplantation); known bleeding disorders, coagulation abnormalities, or sickle cell anemia; active or uncontrolled infection;
11. Other severe physical or psychiatric disorders, or laboratory abnormalities, which in the investigator's judgment may increase risk or interfere with study outcomes, rendering the patient unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIPC Intervention Group; Participants randomized to this group will receive remote ischemic preconditioning (RIPC). After induction of general anesthesia, RIPC will be applied to the upper arm and thigh on the non-arterial cannulation side. The procedure consists of four alternating ischemia-reperfusion cycles, each cycle comprising 5 minutes of cuff inflation (at 200 mmHg, or systolic blood pressure +15 mmHg if systolic blood pressure exceeds 185 mmHg), followed by 5 minutes of cuff deflation for reperfusion. The inflation process alternates, starting with the upper arm. The thigh cuff inflation will begin only after the first upper arm inflation cycle is completed, and this process will repeat in alternating cycles.	Procedure: Remote ischemic preconditioning (RIPC); This intervention is a non-invasive organ protection procedure. After induction of general anesthesia, 4 cycles of remote ischemic preconditioning (RIPC) are applied to the upper arm and thigh on the non-arterial cannulation side. Each cycle consists of 5 minutes of cuff inflation (at 200 mmHg, or systolic blood pressure +15 mmHg if systolic blood pressure exceeds 185 mmHg) to induce ischemia, followed by 5 minutes of cuff deflation for reperfusion. To ensure safety, the cuff inflation cycles alternate between the upper arm and thigh. The procedure aims to activate endogenous protective mechanisms, enhancing the tolerance of vital organs to subsequent ischemic injury during surgery.
Sham Comparator: Control Group; Participants randomized to this group will receive a sham RIPC procedure. The same cuff placement and timing as the experimental group are used, but the cuff is inflated to only 20 mmHg for 5 minutes followed by 5 minutes of deflation, simulating the RIPC procedure without inducing ischemia.	Procedure: Remote ischemic preconditioning (RIPC); This intervention is a non-invasive organ protection procedure. After induction of general anesthesia, 4 cycles of remote ischemic preconditioning (RIPC) are applied to the upper arm and thigh on the non-arterial cannulation side. Each cycle consists of 5 minutes of cuff inflation (at 200 mmHg, or systolic blood pressure +15 mmHg if systolic blood pressure exceeds 185 mmHg) to induce ischemia, followed by 5 minutes of cuff deflation for reperfusion. To ensure safety, the cuff inflation cycles alternate between the upper arm and thigh. The procedure aims to activate endogenous protective mechanisms, enhancing the tolerance of vital organs to subsequent ischemic injury during surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital major adverse outcomes	A composite of major adverse outcomes (binary). Includes: Perioperative all-cause death; Severe post-op complications (Grade III/IV per IAASSG consensus), involving neurological, cardiovascular, respiratory, urinary, gastrointestinal, and other systems.	surgery to discharge or 30 days post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum SOFA-2 Score in First 3 Postoperative Days	The highest (peak) SOFA-2 score recorded during the first 3 days following surgery	From ICU admission (postoperatively) up to postoperative day 3
Operative Time	Total duration of the surgical procedure from skin incision to skin closure, measured in minutes	During the surgical procedure
Duration of Mechanical Ventilation	Total time from the end of surgery until successful extubation, measured in hours. Re-intubation times are included if applicable	From end of surgery until extubation (assessed up to 30 days)
ICU Length of Stay	Total duration of stay in the Intensive Care Unit after surgery, measured in days	From ICU admission after surgery until ICU discharge (assessed up to 30 days)
Hospital Length of Stay	Total duration of hospitalization after surgery, measured in days	From hospital admission for surgery until hospital discharge (assessed up to 30 days)
All-cause mortality	All-cause mortality	30 days, 90 days, 12 months, and every 12 months thereafter, up to 60 months
Postoperative delirium	Incidence of postoperative delirium	From the end of surgery until hospital discharge, assessed up to 30 days postoperatively
Unplanned readmission	The proportion of patients readmitted to the hospital within the follow-up period due to causes related to the original acute type A aortic dissection or its surgical treatment, excluding planned readmissions	30 days, 90 days, 12 months, and every 12 months thereafter, up to 60 months
Incidence of any individual component of the primary composite endpoint at 30 days, 90 days, and 12 months postoperatively	Incidence of each individual adverse event (including death, stroke, renal failure, reoperation, etc.) that constitutes the primary composite endpoint of Major Adverse Outcomes (MAO) at 30 days, 90 days, and 12 months after surgery.	30 days, 90 days, and 12 months postoperatively
Troponin I	To observe changes in troponin I	Within postoperative day 3
Serum Creatinine	To observe changes in serum creatinine	Within postoperative day 3

Collaborators and Investigators

• Sponsor: Fujian Medical University
• Collaborators: The First Affiliated Hospital of Dalian Medical University; Xiamen Cardiovascular Hospital, Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): February 3, 2026

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: ischemia reperfusion injury; emergency surgery; Remote Ischaemic Conditioning; major adverse outcomes
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Reperfusion Injury
• Other Study ID Numbers: A202601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No