Clinical trial NCT05293041: Argipressin's Influence on Blood Loss During Hepatic Resection
Official title: Influence of Argipressin on Blood Loss During Hepatic Resection; a Double-blinded, Randomized Placebo-controlled Trial (ARG-01)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Colon Cancer Liver Metastasis
Inflammatory Response
Vasopressin Causing Adverse Effects in Therapeutic Use
Keywords: hepatic surgery
vasopressin
liver surgery
colon cancer metastasis
transfusion
blood loss
inflammatory response
pain
coagulation
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2022-03-24
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Singel center double-blinded, randomized, placebo-controlled trial.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Blood loss
timeFrame: through surgery, an average of 8 hours
Secondary outcomes:
measure: Blood transfusion
timeFrame: At end of surgery and until postoperative day 2 or 5 respectively
measure: Inflammatory markers-regular
timeFrame: Measured throughout the study until postoperative day 2 (laparoscopic resection) or postoperative day 5 (open resection)
measure: Inflammatory markers- extended
timeFrame: Measured at throughout the study until postoperative day 2.
measure: surgical data
timeFrame: at the end of surgery, approximately 5 hours after start of surgery
measure: Tranexamic Acid
timeFrame: at the end of surgery, approximately 5 hours after start of surgery
measure: CVP (anesthesiological data)
timeFrame: during surgery
measure: Noradrenaline use (anesthesiologigal data)
timeFrame: during surgery
measure: use of diuretics
timeFrame: until postoperative day 1
measure: urine output
timeFrame: until postoperative day 1
measure: postoperative complications
timeFrame: 30 days after surgery
measure: Length of stay
timeFrame: From admission in hospital to discharge, expected time 2-5 days but will be followed until actual discharge, which may be several months.
measure: Plasma Creatinine (change in organ damage markers)
timeFrame: from baseline (before surgery) to postoperative day 2 and 5 respectively.
measure: Urine samples (change in organ damage markers)
timeFrame: from baseline to end of surgery, approximately 5 hours
measure: Cardiac marker (change in organ damage markers)
timeFrame: from baseline to postoperative day 1
measure: Lactate (change in organ damage markers)
timeFrame: from baseline to postoperative day 1
measure: I-FABP (change in organ damage markers)
timeFrame: from baseline to postoperative day 1
Other outcomes:
measure: oral morphine eqivalents
timeFrame: from day of surgery, postoperative day 1,2 and at discharge from hospital (but no longer than post operative day 5)
measure: Numeric Rating Scale (NRS)
timeFrame: Once daily at day of surgery, postoperative day 1 and 2
measure: Clotting Time (CT)
timeFrame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1
measure: Clot Formation time (CFT)
timeFrame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1
measure: Amplitude at 10 minutes (A10)
timeFrame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1
measure: Maximum Clot Firmness (MCF)
timeFrame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1
measure: vWf
timeFrame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1
measure: fVIII
timeFrame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Senior Consultant Anesthesia and Intensive Care, Sahlgrenska University Hospital
name: kristina svennerholm, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: