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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Argipressin | Experimental | Patients will be treated with Empressin® 0.8 U/ml, 0.056 ml/kg/h during surgery. |
|
| Placebo | Placebo Comparator | Patients will receive normal saline 0.056 ml/kg/h during surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Blood loss | 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. | through surgery, an average of 8 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Blood transfusion | Blood transfusion (ml) at the end of surgery and at postoperative day 1 and 2 and 5 respectively. | At end of surgery and until postoperative day 2 or 5 respectively |
| Inflammatory markers-regular |
| Measure | Description | Time Frame |
|---|---|---|
| oral morphine eqivalents | total opioid consumption converted to oral morphine eqivalents (mg) | from day of surgery, postoperative day 1,2 and at discharge from hospital (but no longer than post operative day 5) |
| Numeric Rating Scale (NRS) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| kristina svennerholm, MD PhD | Senior Consultant Anesthesia and Intensive Care, Sahlgrenska University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sahlgrenska University Hospital | Gothenburg | 41345 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41173775 | Derived | Wisen E, Pivodic A, Skagervik A, Rizell M, Bown LS, Ricksten SE, Svennerholm K. Argipressin for prevention of blood loss in hepatic resection: a randomised, placebo-controlled, double-blind trial. Br J Anaesth. 2026 Apr;136(4):1145-1153. doi: 10.1016/j.bja.2025.09.021. Epub 2025 Oct 30. | |
| 37620260 | Derived | 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. |
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Metadata will be shared by the Swedish National Data Service (SND, https://snd.gu.se/en) and selected psedonymised data will be made available on reasonable request, after proper confidentiality and ethics assessment. The extent of data made available will be decided after study closure, and also the time span for availability.
12 months after study closure, and maximum 25 years
Confidentiality and ethics assessment.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 28, 2025 | Mar 3, 2025 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 27, 2023 | Mar 9, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003919 | Diabetes Insipidus |
| D006470 | Hemorrhage |
| D010146 | Pain |
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D001127 | Arginine Vasopressin |
| D001120 | Arginine |
| ID | Term |
|---|---|
| D014667 | Vasopressins |
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
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Singel center double-blinded, randomized, placebo-controlled trial.
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Randomisation will be handled by a nurse not involved in the study, and both the patient, treating physician and nurse, the study nurse and the investigators will be blinded to the study treatment.
|
| 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. |
|
|
Levels of White Blood Cell count, C Reactive Protein, Platelet count and Albumin at the end of surgery and postoperative day 1-5
| Measured throughout the study until postoperative day 2 (laparoscopic resection) or postoperative day 5 (open resection) |
| Inflammatory markers- extended | 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. | Measured at throughout the study until postoperative day 2. |
| surgical data | duration of Pringles manouvre (min), duration of resection phase (min) and surgery (min) | at the end of surgery, approximately 5 hours after start of surgery |
| Tranexamic Acid | use of tranexamic acid (mg) | at the end of surgery, approximately 5 hours after start of surgery |
| CVP (anesthesiological data) | achievement of CVP (central venous pressure) goal (mmHg), as recorded on the Phillips monitor. | during surgery |
| Noradrenaline use (anesthesiologigal data) | Total use of noradrenaline (micrograms/minutes of surgery/ bodyweight) | during surgery |
| use of diuretics | Furosemide use (mg) | until postoperative day 1 |
| urine output | urine output (ml) | until postoperative day 1 |
| postoperative complications | Postoperative complications including death and radicality of resection at 30-day follow up. | 30 days after surgery |
| Length of stay | Length of stay in hospital | From admission in hospital to discharge, expected time 2-5 days but will be followed until actual discharge, which may be several months. |
| Plasma Creatinine (change in organ damage markers) | Change in plasma creatinine (micro-mole/L) | from baseline (before surgery) to postoperative day 2 and 5 respectively. |
| Urine samples (change in organ damage markers) | Change in urine creatinine and urine [TIMP-2] x [IGFBP-7] (quota, no unit) | from baseline to end of surgery, approximately 5 hours |
| Cardiac marker (change in organ damage markers) | Change in hs- TNI (ng/L) | from baseline to postoperative day 1 |
| Lactate (change in organ damage markers) | change in plasma lactate | from baseline to postoperative day 1 |
| I-FABP (change in organ damage markers) | Change in I-FABP (ng/L) | from baseline to postoperative day 1 |
pain assement by Numeric Rating Scale 0-10 (0= no pain, 10= worst pain imaginable), at rest and at activity
| Once daily at day of surgery, postoperative day 1 and 2 |
| Clotting Time (CT) | Clotting Time (CT) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels | before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1 |
| Clot Formation time (CFT) | Clot Formation time (CFT) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels | 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) | Amplitude at 10 minutes (A10) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels | before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1 |
| Maximum Clot Firmness (MCF) | Maximum Clot Firmness (MCF) measured by ROTEM (Thrombelastometry) in Extem, Intem, Fibtem, Heptem channels | before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1 |
| vWf | von Willebrand factor (vWf) | before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1 |
| fVIII | factor VIII | before anesthesia, at end of surgery (assessed up to one hour after closing of the abdomen) and postoperative day 1 |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D010900 | Pituitary Diseases |
| D004700 | Endocrine System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000599 | Amino Acids, Diamino |
| D000601 | Amino Acids, Essential |