Clinical trial NCT03234543: Remote Ischemic Conditioning in Abdominal Surgery
Official title: Remote Ischemic Conditioning (RIC) to Decrease Post-Operative Complications After Major Abdominal Surgery - A Phase IIa Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Laparotomy
Laparoscopy
Retroperitoneal Disease
Pelvis Disease
Pancreatic Diseases
Liver Diseases
Gastrointestinal Disease
Urologic Diseases
Complication of Surgical Procedure
Keywords: Abdominal Surgery
Pre-conditioning
Remote Ischemic Conditioning
Post-Operative Complications
Acute Phase Response
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2017-07-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Comprehensive Complication Index
timeFrame: 30 days after surgery
Secondary outcomes:
measure: Completion all three interventions
timeFrame: Up to 3 days
measure: Hospital days
timeFrame: Up to 30 days
measure: 30-day mortality
timeFrame: Up to 30 days
measure: Plasma complement levels (C2, C4b, C5, C5a, and C5b-9)
timeFrame: Up to 3 days
measure: Plasma cytokines levels (TNF-a, IL - 1, 6, 8 and 10)
timeFrame: Up to 3 days
measure: Plasma acute phase reactant proteins (CRP, alpha-1- acid glycoprotein, FGN, and haptoglobin)
timeFrame: Up to 3 days
measure: Peripheral blood leukocyte gene expression profiles determined by RNA sequencing.
timeFrame: Up to 3 days
Other outcomes:
Locations:
city: Newark
country: United States
facility: University Hospital
state: New Jersey
Study officials:
affiliation: Rutgers-NJMS
name: Baburao Koneru, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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