Argipressin's Influence on Blood Loss During Hepatic Resection

Inflammatory Response Clinical Trial

— ARG-01  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05293041
• Other study ID #: ARG-01
• Status: Recruiting
• Phase: Phase 4
• Start date: March 27, 2022
• Est. completion date: March 2025

Study information

• Verified date: July 2023
• Source: Sahlgrenska University Hospital, Sweden
• Contact: Ellinor Wisen, MD
• Phone: +46313428171
• Email: ellinor.wisen[@]vgregion.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colon Cancer Liver Metastasis
• Colonic Neoplasms
• Hemorrhage
• Inflammatory Response
• Neoplasm Metastasis

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Sweden	Sahlgrenska University Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
Kristina Svennerholm

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	Inflammatory markers-regular	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)
Secondary	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.
Secondary	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
Secondary	Tranexamic Acid	use of tranexamic acid (mg)	at the end of surgery, approximately 5 hours after start of surgery
Secondary	CVP (anesthesiological data)	achievement of CVP (central venous pressure) goal (mmHg), as recorded on the Phillips monitor.	during surgery
Secondary	Noradrenaline use (anesthesiologigal data)	Total use of noradrenaline (micrograms/minutes of surgery/ bodyweight)	during surgery
Secondary	use of diuretics	Furosemide use (mg)	until postoperative day 1
Secondary	urine output	urine output (ml)	until postoperative day 1
Secondary	postoperative complications	Postoperative complications including death and radicality of resection at 30-day follow up.	30 days after surgery
Secondary	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.
Secondary	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.
Secondary	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
Secondary	Cardiac marker (change in organ damage markers)	Change in hs- TNI (ng/L)	from baseline to postoperative day 1
Secondary	Lactate (change in organ damage markers)	change in plasma lactate	from baseline to postoperative day 1
Secondary	I-FABP (change in organ damage markers)	Change in I-FABP (ng/L)	from baseline to postoperative day 1