Remote Ischemic Conditioning in Abdominal Surgery

February 22, 2019 updated by: Baburao Koneru, MD, MPH, Rutgers, The State University of New Jersey

Remote Ischemic Conditioning (RIC) to Decrease Post-Operative Complications After Major Abdominal Surgery - A Phase IIa Trial

This phase II randomized (1:1) controlled trial will examine the effects of remote ischemic conditioning (RIC) on the outcomes of major abdominal surgery. One hundred subjects will be enrolled at a single institution - University Hospital - Newark. The study population are patients undergoing major abdominal surgery (anticipated to be >/= 2 hrs long with a hospital stay >/= 2 days). Subjects in the treatment group will receive lower limb ischemic conditioning at 3 different time points: before surgery, POD 1 and POD 2. The primary outcome is the 30-day comprehensive complications index (CCI). Key secondary outcomes are changes in systemic inflammatory markers in peripheral blood and 30-day mortality.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

STUDY GOALS AND OBJECTIVES:

  1. To obtain preliminary data regarding postoperative complications in subjects undergoing abdominal surgery and receiving remote limb ischemic or sham conditioning.
  2. To test whether remote limb ischemic conditioning (RIC) decreases systemic inflammatory response in patients undergoing major abdominal surgery.

HYPOTHESiS:

The central hypothesis of the research is that pre- and post-operative RIC in patients undergoing major abdominal surgery would decrease the systemic inflammatory response to major abdominal surgery and decrease postoperative complications.

STUDY DESIGN:

A prospective, randomized, double - masked clinical trial of RIC will be conducted in adult patients undergoing major abdominal surgery at University Hospital in Newark, NJ. Participants will be randomized into two groups: RIC and No RIC. RIC will be induced at three time points - the first after anesthesia induction but before commencement of surgery, and the second and the third on post-operative days 1 and 2, respectively. The RIC intervention consists of 5 minutes of inflation of a pneumatic tourniquet placed mid-thigh followed by 5 minutes of deflation, repeated for 3 cycles. The pressure used will be 250 mmHg for the pre-operative intervention. Subsequent tourniquet pressures will be 50 mmHg above the patient's systolic blood pressure. The No RIC group will receive a sham intervention at all the same time points. The thigh tourniquet will be inflated to only 20 mmHg. A Doppler probe will be used to assess pedal arterial flow in both groups. Blood samples will be collected at baseline, 1hr after skin closure, and 1hr after interventions 2 and 3.

STUDY POPULATION:

Adults (> 18 years of age) of both sexes scheduled for elective major abdominal surgery at University Hospital will be considered for inclusion. Major abdominal surgery is defined as peritoneal, retroperitoneal and pelvic surgery expected to last >/= 120 minutes (from incision to closure) with an expected hospital stay >/= 2 days. A list of surgeries considered for inclusion is included as Appendix A. Additional operations will be considered for inclusion if the study team and primary surgical team both agree that the procedure is a major abdominal surgery and that the duration of surgery is likely to be > 2 hours.

RISKS AND BENEFITS

  1. Risks to Subjects During inflation of the tourniquet in awake patients (post-op), there is a risk of pain secondary to tourniquet inflation. The investigators believe this risk is small, and if it occurs, the patient will have the option to discontinue the intervention.

    There is a theoretical risk of injury to the limb receiving the RIC stimulus. However, such occurrences have not been reported to date in other clinical studies.

    During collection of blood samples, there is a theoretical risk of bleeding from the venipuncture site; however this risk is no greater than routine blood draw. The amount of blood drawn for study purposes will be small (less than 50 mL total anticipated).

  2. Benefits to Subjects The anticipated benefit to subjects is fewer complications after major abdominal surgery. However, no such benefit may accrue. In addition, the study is expected to provide valuable information regarding how RIC might modulate stress response to major surgery.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Newark, New Jersey, United States, 07101
        • University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adults (> 18 years of age)
  2. Both genders
  3. Undergoing major abdominal surgery as above
  4. Elective surgeries
  5. Both outpatients and in-hospital patients
  6. Post-op length of stay expected to be at least 2 days by the primary surgical service

Exclusion Criteria:

  1. Subjects with lower extremity paralysis
  2. Lower extremity amputees
  3. Known, documented peripheral arterial disease
  4. Body mass index > 45
  5. Pregnancy
  6. Trauma patients
  7. Organ transplant recipients
  8. Prior major surgery during current hospitalization (for instance, a patient undergoing re-laparotomy for a complication from a previous procedure)

  9. Patient taking sulfonylureas or nitrates prior to or during admission (listed in Appendix B)

    a. These subjects are excluded because sulfonylureas are shown to abrogate the RIC effect whereas nitrates are shown to mimic the RIC effect in animal models.

  10. Non-elective surgeries (urgent or emergent surgeries)
  11. General surgical procedures with no planned intra-abdominal component

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Remote Ischemic Conditioning
The RIC intervention consists of 5 minutes of inflation of a pneumatic tourniquet placed mid-thigh followed by 5 minutes of deflation, repeated for 3 cycles. The pressure used will be 250 mmHg for the pre-operative intervention. Subsequent tourniquet pressures will be 50 mmHg above the patient's systolic blood pressure.
Procedure: Remote ischemic conditioning
Placement of blood pressure cuff to lower extremity in order to induce temporary and reversible ischemia.
SHAM_COMPARATOR: No Remote Ischemic Conditioning
The No RIC group will receive a sham intervention at all the same time points. The thigh tourniquet will be inflated to only 20 mmHg (to mask the intervention from the subject).
Procedure: No Remote ischemic conditioning
Placement of blood pressure cuff to lower extremity with minimal inflation without inducing ischemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comprehensive Complication Index
Time Frame: 30 days after surgery
The CCI, a validated and scaled score of all surgical complications (range 0 [no complications] to 100 [death]) will be computed for each subject using the publically available website, http://www.assessurgery.com/.
30 days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Completion all three interventions
Time Frame: Up to 3 days
Proportions of subjects completing all three research interventions
Up to 3 days
Hospital days
Time Frame: Up to 30 days
Number of days to discharge from the hospital after surgery
Up to 30 days
30-day mortality
Time Frame: Up to 30 days
Proportions of patients dying within 30 days after surgery
Up to 30 days
Plasma complement levels (C2, C4b, C5, C5a, and C5b-9)
Time Frame: Up to 3 days
Measured at baseline, an hour after skin closure, completion of second and third research intervention
Up to 3 days
Plasma cytokines levels (TNF-a, IL - 1, 6, 8 and 10)
Time Frame: Up to 3 days
Plasma cytokine levels at baseline, an hour after skin closure, completion of second and third research intervention
Up to 3 days
Plasma acute phase reactant proteins (CRP, alpha-1- acid glycoprotein, FGN, and haptoglobin)
Time Frame: Up to 3 days
Measured at baseline, an hour after skin closure, completion of second and third research intervention
Up to 3 days
Peripheral blood leukocyte gene expression profiles determined by RNA sequencing.
Time Frame: Up to 3 days
Measured at baseline, an hour after skin closure, completion of second and third research intervention
Up to 3 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rutgers, The State University of New Jersey

Investigators

  • Principal Investigator: Baburao Koneru, MD, MPH, Rutgers-NJMS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 8, 2017

Primary Completion (ANTICIPATED)

June 15, 2019

Study Completion (ANTICIPATED)

June 15, 2020

Study Registration Dates

First Submitted

July 25, 2017

First Submitted That Met QC Criteria

July 28, 2017

First Posted (ACTUAL)

July 31, 2017

Study Record Updates

Last Update Posted (ACTUAL)

February 25, 2019

Last Update Submitted That Met QC Criteria

February 22, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro20160001420

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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