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NCT Number: NCT05293041

Argipressin's Influence on Blood Loss During Hepatic Resection

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.

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Key information

Conditions

Colon Cancer Liver Metastasis Cardiovascular Diseases Diabetes Insipidus Embolism and Thrombosis Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hemorrhage Inflammatory Response Kidney Diseases Male Urogenital Diseases Neurologic Manifestations Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Pituitary Diseases Signs and Symptoms Thrombosis Urogenital Diseases Urologic Diseases Vascular Diseases Vasopressin Causing Adverse Effects in Therapeutic Use

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant planned for hepatic resection (open or laparoscopic, regardless of indication for surgery).
  • Age ≥18 years.
  • ASA class I-III.
  • Signed informed consent form

Exclusion criteria

  • Participant does not understand the given information, and/ or cannot give written informed consent.
  • 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.
  • Terminal kidney failure (estimated preoperative GFR< 15 ml/min)
  • Pregnancy or lactation.
  • Known allergy to Empressin®.
  • Patient included in other interventional study, interacting with the endpoints in the present study, or previous randomization in this study.
  • Hyponatremia (S-Na < 130 mmol/L)
  • Patient considered ineligible for other surgical or medical reason.
  • 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.

Treatment and study plan

Argipressin

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.

Other names: Arg

Placebo

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.

Other names: control

Primary outcomes

  1. Blood loss

    Time frame: through surgery, an average of 8 hours

    Blood loss at the end of surgery, measured according to the investigator's instructions, by visual assessment of suction devises and gauze, and subtraction of ascites and irrigation fluids.

Secondary outcomes

  1. Blood transfusion

    Time frame: At end of surgery and until postoperative day 2 or 5 respectively

    Blood transfusion (ml) at the end of surgery and at postoperative day 1 and 2 and 5 respectively.

  2. Inflammatory markers-regular

    Time frame: Measured throughout the study until postoperative day 2 (laparoscopic resection) or postoperative day 5 (open resection)

    Levels of White Blood Cell count, C Reactive Protein, Platelet count and Albumin at the end of surgery and postoperative day 1-5

  3. Inflammatory markers- extended

    Time frame: Measured at throughout the study until postoperative day 2.

    Levels of Interleukin (IL)-1 Beta, IL-6, IL-8, IL-10, Monocyte chemoattractant protein-1, Stromal Cell-Derived Factor-1 alpha, Intercellular Adhesion Molecule, Complement (C) 3a, C5b-9 at the end of surgery and postoperative day 1 and 2.

  4. surgical data

    Time frame: at the end of surgery, approximately 5 hours after start of surgery

    duration of Pringles manouvre (min), duration of resection phase (min) and surgery (min)

  5. Tranexamic Acid

    Time frame: at the end of surgery, approximately 5 hours after start of surgery

    use of tranexamic acid (mg)

  6. CVP (anesthesiological data)

    Time frame: during surgery

    achievement of CVP (central venous pressure) goal (mmHg), as recorded on the Phillips monitor.

  7. Noradrenaline use (anesthesiologigal data)

    Time frame: during surgery

    Total use of noradrenaline (micrograms/minutes of surgery/ bodyweight)

  8. use of diuretics

    Time frame: until postoperative day 1

    Furosemide use (mg)

  9. urine output

    Time frame: until postoperative day 1

    urine output (ml)

  10. postoperative complications

    Time frame: 30 days after surgery

    Postoperative complications including death and radicality of resection at 30-day follow up.

  11. Length of stay

    Time frame: From admission in hospital to discharge, expected time 2-5 days but will be followed until actual discharge, which may be several months.

    Length of stay in hospital

  12. Plasma Creatinine (change in organ damage markers)

    Time frame: from baseline (before surgery) to postoperative day 2 and 5 respectively.

    Change in plasma creatinine (micro-mole/L)

  13. Urine samples (change in organ damage markers)

    Time frame: from baseline to end of surgery, approximately 5 hours

    Change in urine creatinine and urine [TIMP-2] x [IGFBP-7] (quota, no unit)

  14. Cardiac marker (change in organ damage markers)

    Time frame: from baseline to postoperative day 1

    Change in hs- TNI (ng/L)

  15. Lactate (change in organ damage markers)

    Time frame: from baseline to postoperative day 1

    change in plasma lactate

  16. I-FABP (change in organ damage markers)

    Time frame: from baseline to postoperative day 1

    Change in I-FABP (ng/L)

Other outcomes

  1. oral morphine eqivalents

    Time frame: from day of surgery, postoperative day 1,2 and at discharge from hospital (but no longer than post operative day 5)

    total opioid consumption converted to oral morphine eqivalents (mg)

  2. Numeric Rating Scale (NRS)

    Time frame: Once daily at day of surgery, postoperative day 1 and 2

    pain assement by Numeric Rating Scale 0-10 (0= no pain, 10= worst pain imaginable), at rest and at activity

  3. Clotting Time (CT)

    Time frame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1

    Clotting Time (CT) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels

  4. Clot Formation time (CFT)

    Time frame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1

    Clot Formation time (CFT) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels

  5. Amplitude at 10 minutes (A10)

    Time frame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1

    Amplitude at 10 minutes (A10) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels

  6. Maximum Clot Firmness (MCF)

    Time frame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1

    Maximum Clot Firmness (MCF) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels

  7. vWf

    Time frame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1

    von Willebrand factor (vWf)

  8. fVIII

    Time frame: before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1

    factor VIII

Sponsors and collaborators

Lead sponsor

Kristina Svennerholm

Other

Registry information

Official study title

Influence of Argipressin on Blood Loss During Hepatic Resection; a Double-blinded, Randomized Placebo-controlled Trial (ARG-01)

Acronym: ARG-01

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Mar 24, 2022
Registry last updated
Mar 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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