Ischemic Preconditioning at a Distance in Liver Surgery (HEPATOPROTECT)

Randomized, Single-blind Study of Remote Ischemic Preconditioning in Hepatectomies

During hepatic transection, it exists a high risk of perioperative blood loss. The haemorrhage and its consequences (hypovolemia and blood transfusion) might impact the short and long term morbidity The vascular control by hepatic pedicle clamping (Pringle's maneuver) or total hepatic vascular exclusion, helps minimizing blood loss and leads to a more extensive hepatic resection.

Side effects of vascular control result of ischemia-reperfusion injury (IRI) : these reperfusion lesions results of different mechanisms than those responsible for the ischemic one. IRI cause lesions and postoperative dysfunction of the remaining liver.

Among strategies to reduce the adverse effects of IRI : ischaemic preconditioning (IPC) has been described. It can be either mechanical (intermittent hepatic pedicle clamping) or pharmacological (sevoflurane inhalation).

Short intermittent vascular occlusions in a organ might produce a resistance to a longer ischaemic period. It is certainly a physiological organ adaptation to tissue hypoxemia, which has a therapeutic potential when targeted.

During liver resection, ischaemic preconditioning is realised with periods of hepatic pedicle clamping and unclamping. It decrease morbidity and mortality and prevent postoperative hepatocellular insufficiency due to clamping and IRI at day 5.

Ischaemic preconditioning may also be applied remotely. Indeed, it is shown that short ischaemic periods in a target organ can also have a protective effect on distant others. This mechanism involve three signalling pathways : neuronal , humoral and systemic pathways.

In a previous randomized study, Kanoria and al, demonstrated that the remote ischaemic preconditioning group has shown significant lower rates of serum transaminases and higher liver clearance (spectrophotometry method) than the control group.

A latest study, measuring postoperative prothrombin rates has shown improved liver recovery due to halogen agents such as sevoflurane.

Study Overview

• Status: Completed
• Conditions: Liver Diseases
• Intervention / Treatment: Procedure: pneumatic tourniquet; Other: No inflation

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • Hop Claude Huriez Chu Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Scheduled carcinogenic laparoscopy or laparotomy liver resection
• Insured under the social security system
• Inclined to comply to the study protocol and its duration.

Exclusion Criteria:

• Patient under guardianship
• Pregnancy or breastfeeding
• Severe lower limb vascular disease
• Emergency surgery
• Contraindication of a treatment from the protocol
• Psychological disorder with difficulty to accede the protocol
• Absence of written informed consent
• Refusal to sign the protocol
• Non-registration to the social security system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Inflation of a pneumatic tourniquet	Procedure: pneumatic tourniquet; a pneumatic tourniquet around 200 mmHg after venous chase of the lower limb, during 5 minutes then deflated. Repeated twice after general anaesthesia and prior to incision.
SHAM_COMPARATOR: No inflation; No inflation of the pneumatic tourniquet placed on the lower limb	Other: No inflation; No inflation of the pneumatic tourniquet placed on the lower limb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indocyanine green clearance	Indocyanine green clearance (%/min) by indocyanine green retention, measured with Limon pulse spectrophotometry method.	at 5 days after liver resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum transaminases rates		at day 1,day 3 and day 5 post-hepatectomy.
Prothrombin rate		at day 5 post-hepatectomy.
the Kidney Disease: Improving Global Outcomes (KDIGO) score	The score varies from 1 to 4.	at day 1,day 3 and day 5 post-hepatectomy.
the Clavien & Dindo score	this classification in order to rank a post operative complications. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V)	at day 30 post-hepatectomy
duration of stay in the hospital.		at day 30 post-hepatectomy

Collaborators and Investigators

• Sponsor: University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 16, 2019
• Primary Completion (ACTUAL): January 6, 2020
• Study Completion (ACTUAL): January 6, 2020

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (ACTUAL): November 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Remote ischemic preconditioning; liver resection; liver clearance.
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 2017_66; 2018-A03038-47 (OTHER: ID-RCB number, ANSM)

Drug and device information, study documents

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