Influence of Argipressin on blood loss during liver resection; a double-blinded, randomized, placebo-controlled trial (ARG-01)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Mar 2022 → 17 Feb 2025

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514332-25-00

EudraCT number

2021-001806-32

ClinicalTrials.gov

NCT05293041

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To determine if infusion of Argipressin during hepatic resection surgery reduces blood loss compared to placebo.

Secondary objectives 2

1. To determine if infusion of Argipressin during hepatic resection surgery reduces the need of transfusions during and after surgery, compared to placebo.
2. To determine if infusion of Argipressin during hepatic resection surgery mitigates the postoperative inflammatory response, compared to placebo.

Conditions and MedDRA coding

Hepatic resection due to primary malignant disease, metastasis or benign tumour

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participant planned for hepatic resection (open or laparoscopic, regardless of indication for surgery).
2. Age ≥18 years.
3. American Society of Anaesthesiologists (ASA) class I-III.
4. Signed informed consent form.

Exclusion criteria 10

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.
10. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Blood loss (ml) at the end of surgery, measured according to the investigator’s instructions, by visual assessment of suction devices and gauze, and subtraction of ascites and irrigation fluids.

Secondary endpoints 12

1. Blood transfusion (ml) at the end of surgery, and at postoperative day 1 and postoperative day 2 or 5, respectively as well as plasma and thrombocytes day 2/5.
2. Levels of WBC, CRP, PLT and Albumin at the end of surgery and postoperative day 1-5.
3. Levels of IL-1b IL-6, IL-8, IL-10, MCP-1, SDF-1a, ICAM, C3a, C5b-9 at the end of surgery and postoperative day 1 and 2.
4. ROTEM, vWF activity, factor VIII at the end of surgery and postoperative day 1.
5. Plasma creatinine will be controlled at postoperative day 1, 2 and 5. Urine [TIMP-2] x [IGFBP-7] will be controlled after surgery.
6. Hs-TNI will be controlled at the end of surgery and at postoperative day 1.
7. Arterial lactate will be controlled at the end of surgery, at three hours after surgery and at postoperative day 1.
8. IFABP will be controlled at three hours after surgery and postoperative day one.
9. Vasopressor use during surgery, achievement of CVP goal, total urine output and use of furosemide at postoperative day 1.
10. Measurements of mean arterial blood pressure (MAP), heart rate, CVP and Cardiac Index (if applicable), as well as assessment of capillary refill time in digits at the end of surgery.
11. Total time of surgical hepatic occlusion and radicality of resection, as well as use of TXA.
12. Length of stay in hospital and postoperative complications documented at postoperative day 30.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Kristina Svennerholm

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Kristina Svennerholm

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications