Evaluation of Postoperative Ascites After Somatostatin Infusion Following Hepatectomy for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Most patients undergoing hepatectomy for hepatocellular carcinoma (HCC) suffer from underlying liver disease and are exposed to the risk of postoperative ascites, with subsequent morbidity, liver and renal failure, the need for specific treatments and prolonged hospital stay. Postoperative ascites is favored by an imbalance between portal venous inflow and the diminished hepatic venous outflow. Finding a reversible, non-invasive method for modulating the portal inflow would be of interest: it could be used temporarily during the early postoperative course to prevent acute portal hypertension. Somatostatin, a well-known drug already used in several indications, may limit the risk of postoperative ascites and liver failure by decreasing portal pressure after hepatectomy for HCC in patients with underlying liver disease.

Official Title
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Evaluation of Postoperative Ascites After Somatostatin Infusion Following Hepatectomy for Hepatocellular Carcinoma: Multicenter Randomized Double-blind Placebo Controlled Trial (SOMAPROTECT01)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: somatostatin infusion
* Drug: placebo infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with HCC diagnosed by histology or by imaging findings according to the Barcelona Clinic Liver Cancer Group Patients with a single or multiple HCCs deemed to be resectable with a curative intent at the preoperative evaluation Patients for whom an indication for hepatectomy has been decided and approved by multidisciplinary board: by laparotomy by coelioscopy with resection of at least 2 liver segments Patients with any underlying liver disease with or without proven cirrhosis, regarding histological features (including F2-F3-F4 fibrosis with or without cirrhosis) or with other evidence of a diseased liver if no biopsy has been performed preoperatively (dysmorphic liver or evidence of portal hypertension at imaging findings, oesophageal varices at endoscopy) Age ≥ 18 years Patients with ability to understand and sign a written inform consent form Patients who will be available for follow-up Exclusion Criteria: Patients participating in another interventional research in progress or including an exclusion period still in progress at pre-inclusion (except interventional research with minimal risks and constraints that do not interfere with the judgement criteria of the study according to the judgement of the coordinating investigator). Patients with evidence of a healthy liver at biopsy Disease-associated non-inclusion criteria include: Another histologic type of hepatic tumor besides HCC Distant extra-hepatic metastases, including peritoneal carcinomatosis The existence of complete portal thrombosis of the main portal trunk Operative technique-associated non-inclusion criteria include: - Indication of coelioscopy with resection of less than 2 liver segments

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>postoperative somatostatin infusion during 5 days at 6mg/day, followed by one day at 3mg/day | Drug: somatostatin infusion<br>* postoperative somatostatin infusion during 5 days at 6mg/day, followed by one day at 3mg/day.<br>|
| Placebo Comparator: Control group<br>Placebo infusion (50ml of 0.9% NaCl/day) during 6 days | Drug: placebo infusion<br>* Placebo infusion (50ml of 0.9% NaCl/day) during 6 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| presence of postoperative ascites during the postoperative course | The presence of postoperative ascites during the postoperative course defined by: ≥500 ml / 24h of fluid in the drains during at least 3 days. Or ascites requiring puncture or drainage | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of ascites | Number of days with ≥ 500ml / 24h of ascites | Day 90 | 
| Volume of ascites | Total ascites volume | Day 90 | 
| postoperative morbidity | Postoperative morbidity according to Dindo-Clavien | Day 90 | 
| Postoperative morbidity on Liver failure | Presence and severity of hepatic failure according to International Study Group of Liver Surgery (ISGLS) | Day 90 | 
| Postoperative morbidity on Renal failure | Presence and severity of renal failure according to RIFLE scale (RIFLE: Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Hepatectomy, Ascites, Somatostatin