Argipressin's Influence on Blood Loss During Hepatic Resection

NCT ID: NCT05293041

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-27
• Study Completion Date: 2025-02-17

Brief Summary

Infusion of Argipressin during hepatic resection surgery may reduce blood loss. It may also reduce transfusion requirements, and mitigate the perioperative inflammatory response compared to placebo. Subjects will be randomized to infusion of Argipressin or placebo during surgery. Blood loss, transfusion requirements, surgical data including length of stay in hsopital, inflammatory markers and markers of renal- intestinal- and cardiac injury will be assessed. Two sub-studies has been added; one for evaluation of coagulation function, and one for assessment of pain scores and morphine consumption.

Detailed Description

Hepatic resection is a major surgical intervention with high risk of substantial blood loss. The surgical means to reduce blood loss may impair perfusion and induce intestinal congestion. If blood flow to the liver can be influenced by pharmacological means, blood loss and transfusion requirements may be reduced. Moreover, the inflammatory system is involved in cancer development, and the anti-inflammatory properties of Argipressin may decrease the inflammatory response after hepatic surgery.

Argipressin is an endogenous substance, and part of the body's response to stress and trauma. Argipressin affects V1-receptors to produce vasoconstriction. It is also involved in inflammatory reactions and affects platelets.

Patients will be stratified according to planned type of surgery (open/laparoscopic) and planned extent of resection, and randomized to etiher infusion of Argipressin or placebo (normal saline) during surgery. In all other aspects, the participants will be treated according to the institution protocol for hepatic resection. The study drug will be started as soon as the central line is placed, and discontinued at the end of surgery. Hemodynamic data will be collected during surgery, and blood and urine-samples will be obtained during and after surgery for analysis of inflammatory markers and markers of organ injury.

Conditions

Colon Cancer Liver Metastasis; Inflammatory Response; Vasopressin Causing Adverse Effects in Therapeutic Use

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Argipressin

Patients will be treated with Empressin® 0.8 U/ml, 0.056 ml/kg/h during surgery.

Group Type: EXPERIMENTAL

Argipressin

Intervention Type: DRUG

Infusion of Argipressin 0.8 U/ml, 0.056 ml/kg/h will be started as soon as the central line is placed, and continued until the end of surgery in the treatment arm.

Placebo

Patients will receive normal saline 0.056 ml/kg/h during surgery.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Infusion of Normal Saline 0.056 ml/kg/h will be started as soon as the central line is placed, and continued until the end of surgery in the placebo arm.

Interventions

Argipressin

Infusion of Argipressin 0.8 U/ml, 0.056 ml/kg/h will be started as soon as the central line is placed, and continued until the end of surgery in the treatment arm.

Intervention Type: DRUG

Placebo

Infusion of Normal Saline 0.056 ml/kg/h will be started as soon as the central line is placed, and continued until the end of surgery in the placebo arm.

Intervention Type: DRUG

Other Intervention Names

Arg; control

Eligibility Criteria

Inclusion Criteria

1. Participant planned for hepatic resection (open or laparoscopic, regardless of indication for surgery).

2. Age ≥18 years.

3. ASA class I-III.

4. Signed informed consent form

Exclusion Criteria

1. Participant does not understand the given information, and/ or cannot give written informed consent.

2. Simultaneous operation of tumor with other localization, or surgery for superficial single hepatic tumor less than 2 cm, expected to be of short duration and with minimal blood loss.

3. Terminal kidney failure (estimated preoperative GFR< 15 ml/min)

4. Pregnancy or lactation.

5. Known allergy to Empressin®.

6. Patient included in other interventional study, interacting with the endpoints in the present study, or previous randomization in this study.

7. Hyponatremia (S-Na < 130 mmol/L)

8. Patient considered ineligible for other surgical or medical reason.

9. Present infection. Patients with systemic inflammatory disease, inflammatory bowel disease or preoperative corticosteroid treatment will not be eligible for the subgroups where cytokines and interleukins are investigated.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kristina Svennerholm

OTHER

Sponsor Role: lead

Responsible Party

Kristina Svennerholm

Principal investigator, MD, PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

kristina svennerholm, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Senior Consultant Anesthesia and Intensive Care, Sahlgrenska University Hospital

Locations

Sahlgrenska University Hospital

Gothenburg, , Sweden

Countries

Sweden

References

Wisen E, Kvarnstrom A, Sand-Bown L, Rizell M, Pivodic A, Ricksten SE, Svennerholm K. Argipressin for prevention of blood loss during liver resection: a study protocol for a randomised, placebo-controlled, double-blinded trial (ARG-01). BMJ Open. 2023 Aug 24;13(8):e073270. doi: 10.1136/bmjopen-2023-073270.

Reference Type: DERIVED

PMID: 37620260 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ARG-01

Identifier Type: -

Identifier Source: org_study_id