Argipressin's Influence on Blood Loss During Hepatic Resection (ARG-01)

Kristina Svennerholm

Status and phase: Completed; Phase 4

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

Treatments: Drug: Placebo; Drug: Argipressin

Study type: Interventional

Funder types: Other

Identifiers

NCT05293041

ARG-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 248 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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248 participants in 2 patient groups, including a placebo group

Argipressin

Experimental group

Description:

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

Treatment:

Drug: Argipressin

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo