Remote Ischemic Conditioning in Abdominal Surgery

NCT03234543 | Unknown

• 1 other identifier: Pro20160001420
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Comprehensive Complication Index

  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 Outcomes (7)

• Completion all three interventions

  Up to 3 days

• Hospital days

  Up to 30 days

• 30-day mortality

  Up to 30 days

• Plasma complement levels (C2, C4b, C5, C5a, and C5b-9)

  Up to 3 days

• Plasma cytokines levels (TNF-a, IL - 1, 6, 8 and 10)

  Up to 3 days

Study Arms (2)

Remote Ischemic Conditioning

EXPERIMENTAL

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

No Remote Ischemic Conditioning

SHAM COMPARATOR

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

Interventions

Remote ischemic conditioning PROCEDURE

Placement of blood pressure cuff to lower extremity in order to induce temporary and reversible ischemia.

Remote Ischemic Conditioning

No Remote ischemic conditioning PROCEDURE

Placement of blood pressure cuff to lower extremity with minimal inflation without inducing ischemia.

No Remote Ischemic Conditioning

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Subjects with lower extremity paralysis
• Lower extremity amputees
• Known, documented peripheral arterial disease
• Body mass index \> 45
• Pregnancy
• Trauma patients
• Organ transplant recipients
• Prior major surgery during current hospitalization (for instance, a patient undergoing re-laparotomy for a complication from a previous procedure)
• 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.
• Non-elective surgeries (urgent or emergent surgeries)
• General surgical procedures with no planned intra-abdominal component

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

Study Sites (1)

University Hospital

Newark, New Jersey, 07101, United States

Location

Related Publications (18)

• Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013 Jul;258(1):1-7. doi: 10.1097/SLA.0b013e318296c732.

  PMID: 23728278 BACKGROUND

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• Lausevic Z, Lausevic M, Trbojevic-Stankovic J, Krstic S, Stojimirovic B. Predicting multiple organ failure in patients with severe trauma. Can J Surg. 2008 Apr;51(2):97-102.

  PMID: 18377749 BACKGROUND

• Kvarnstrom AL, Sarbinowski RT, Bengtson JP, Jacobsson LM, Bengtsson AL. Complement activation and interleukin response in major abdominal surgery. Scand J Immunol. 2012 May;75(5):510-6. doi: 10.1111/j.1365-3083.2012.02672.x.

  PMID: 22229650 BACKGROUND

• Kvarnstrom A, Sokolov A, Swartling T, Kurlberg G, Mollnes TE, Bengtsson A. Alternative pathway activation of complement in laparoscopic and open rectal surgery. Scand J Immunol. 2012 Jul;76(1):49-53. doi: 10.1111/j.1365-3083.2012.02702.x.

  PMID: 22486843 BACKGROUND

• Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation. 1997 Sep 2;96(5):1641-6. doi: 10.1161/01.cir.96.5.1641.

  PMID: 9315559 BACKGROUND

• Leung CH, Caldarone CA, Wang F, Venkateswaran S, Ailenberg M, Vadasz B, Wen XY, Rotstein OD. Remote Ischemic Conditioning Prevents Lung and Liver Injury After Hemorrhagic Shock/Resuscitation: Potential Role of a Humoral Plasma Factor. Ann Surg. 2015 Jun;261(6):1215-25. doi: 10.1097/SLA.0000000000000877.

  PMID: 25185480 BACKGROUND

• Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V, Downey GP, Liu PP, Cukerman E, Coles JG, Redington AN. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004 Sep 16;19(1):143-50. doi: 10.1152/physiolgenomics.00046.2004. Epub 2004 Aug 10.

  PMID: 15304621 BACKGROUND

• Pang T, Zhao Y, Zhang NR, Jin SQ, Pan SQ. Transient limb ischemia alters serum protein expression in healthy volunteers: complement C3 and vitronectin may be involved in organ protection induced by remote ischemic preconditioning. Oxid Med Cell Longev. 2013;2013:859056. doi: 10.1155/2013/859056. Epub 2013 Dec 2.

  PMID: 24363825 BACKGROUND

• Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.

  PMID: 18456674 BACKGROUND

• Ali ZA, Callaghan CJ, Lim E, Ali AA, Nouraei SA, Akthar AM, Boyle JR, Varty K, Kharbanda RK, Dutka DP, Gaunt ME. Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation. 2007 Sep 11;116(11 Suppl):I98-105. doi: 10.1161/circulationaha.106.679167.

  PMID: 17846333 BACKGROUND

• Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.

  PMID: 23035060 BACKGROUND

• Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P, Haeberle H, Gorlich D, Kellum JA, Meersch M; RenalRIPC Investigators. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015 Jun 2;313(21):2133-41. doi: 10.1001/jama.2015.4189.

  PMID: 26024502 BACKGROUND

• Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schon J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K; RIPHeart Study Collaborators. A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. N Engl J Med. 2015 Oct 8;373(15):1397-407. doi: 10.1056/NEJMoa1413579. Epub 2015 Oct 5.

  PMID: 26436208 BACKGROUND

• Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.

  PMID: 26436207 BACKGROUND

• Gonzalez NR, Hamilton R, Bilgin-Freiert A, Dusick J, Vespa P, Hu X, Asgari S. Cerebral hemodynamic and metabolic effects of remote ischemic preconditioning in patients with subarachnoid hemorrhage. Acta Neurochir Suppl. 2013;115:193-8. doi: 10.1007/978-3-7091-1192-5_36.

  PMID: 22890668 BACKGROUND

• Li S, Ma C, Shao G, Esmail F, Hua Y, Jia L, Qin J, Ren C, Luo Y, Ding Y, Borlongan CV, Ji X. Safety and Feasibility of Remote Limb Ischemic Preconditioning in Patients With Unilateral Middle Cerebral Artery Stenosis and Healthy Volunteers. Cell Transplant. 2015;24(9):1901-11. doi: 10.3727/096368914X683520. Epub 2014 Jul 30.

  PMID: 25198862 BACKGROUND

• Bilgin-Freiert A, Dusick JR, Stein NR, Etchepare M, Vespa P, Gonzalez NR. Muscle microdialysis to confirm sublethal ischemia in the induction of remote ischemic preconditioning. Transl Stroke Res. 2012 Jun;3(2):266-72. doi: 10.1007/s12975-012-0153-1. Epub 2012 Apr 10.

  PMID: 24323782 BACKGROUND

MeSH Terms

Conditions

Pancreatic Diseases; Liver Diseases; Gastrointestinal Diseases; Urologic Diseases; Acute-Phase Reaction

Condition Hierarchy (Ancestors)

Digestive System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Baburao Koneru, MD, MPH

  Rutgers-NJMS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The study will be conducted in a double-masked fashion. Investigative team member/s that will carry out randomization and administer the intervention will not be involved in evaluation of clinical and laboratory outcomes. The primary surgical team, nurses, and any consulting services caring for the patient will be unaware of the group assignment. Other care providers will not be informed of the group assignment. Outcome assessors will not be involved in randomization and administration of the RIC intervention. Adequate steps are in place to mask the outcome assessors (clinical and laboratory) from knowing group assignment. Subjects will be masked from recognizing which group they are in in the following manner: a) Subjects will not be informed of the group assignment throughout their participation in the study; b) subjects randomized to No RIPC will have a tourniquet placed on the thigh and inflated.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Model Details: 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.

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 31, 2017
• Study Start: October 8, 2017
• Primary Completion: June 15, 2019
• Study Completion: June 15, 2020
• Last Updated: February 25, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)