Clinical trial NCT00151671: Effect of a Perioperative Oral Nutritional Supplementation on Patients Undergoing Hepatic Surgery for Liver Cancer
Official title: Prospective, Randomized, Double Blind, Placebo-Controlled Study Evaluating the Effect of Oral Immune-Enhancing Nutritional Supplement on Hepatic Function After Liver Resection for Primary or Secondary Cancer on Cirrhosis or Liver Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Liver Cancer
Hepatocellular Carcinoma
Cirrhosis
Liver Fibrosis
Keywords: Surgery
Liver Cancer
Cirrhosis
Nutrition
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Novartis
First posted: 2005-09-09
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Cirrhotic patients undergoing hepatic resection have a mortality rate near 10%, and 30 to 70% of them develop severe complications. These failures are mainly due to hepatic insufficiency. Studies have already shown benefits of oral nutritional supplements in ORL, digestive, and cardiac surgery. We aimed to ascertain whether this nutritional, immune-enhancing supplementation, administered 7 days before and 3 days after surgery, could improve liver function and postoperative host defences in patients with liver cancer resection.

Detailed description: In patients undergoing hepatic resection for liver cancer (with cirrhosis or fibrosis liver), mortality rate can reach 10% and morbidity (ascites, icteria, infections) 70%. These complications are mainly due to hepatic insufficiency: surgery leaves a reduced parenchyma, with oxidative stress lesions due to reperfusion injury. A good preoperative nutritional state has been shown to reduce complications and mortality. This can be amplified by preoperative nutrition with supplements containing L-arginin, ω3 polyunsaturated fatty acids, and nucleotides which boost immune responses, resistance to infections and liver function recovery. In this context, the study randomly assigns 50 patients who were scheduled to undergo hepatic resection, to receive either an oral immune-enhancing nutritional supplement or a placebo, for the 7 last preoperative and the first 3 postoperative days. The aim of the study is to evaluate the effects of this supplementation on liver function, immunity, and incidence of infections after surgery.

Eligibility criteria: Inclusion Criteria:

* Adult over 18 years
* Hepatectomy of at least 2 segments
* For primary or secondary cancer
* With cirrhosis (Child Pugh \<8) or liver fibrosis (fibrosis score of 3)
* Informed written consent

Exclusion Criteria:

* Pregnancy
* Recent weight loss of more than 10% of body weight
* Immunological deficiency
* Portal or hepatic arterial thrombosis
* Biliary duct dilation

Primary outcomes:
measure: Factor V at day 3 after surgery
timeFrame: day 3
Secondary outcomes:
measure: Liver regeneration kinetics (bile production at days 1, 3, 5 and 7;factor V, γ-glutathione transferase, α-foetoprotein at days 1, 3, 5, 7, 10 and 30; liver volume at days 10 and 30
timeFrame: days 1, 3, 5, 7, 10 and 30
measure: Immunological biomarkers
timeFrame: Within 30 days
measure: Infections
timeFrame: Within 30 days
Other outcomes:
Locations:
city: Rennes
country: France
facility: Service de Réanimation Chirurgicale - Hôpital Pontchaillou
Study officials:
affiliation: Rennes University Hospital
name: Yannick Mallédant, MD
role: STUDY_DIRECTOR
affiliation: Rennes University Hospital
name: Eric Bellissant, MD, PhD
role: STUDY_CHAIR
affiliation: Rennes University Hospital
name: Philippe Seguin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Karim Boudjema, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tepaske R, Velthuis H, Oudemans-van Straaten HM, Heisterkamp SH, van Deventer SJ, Ince C, Eysman L, Kesecioglu J. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial. Lancet. 2001 Sep 1;358(9283):696-701. doi: 10.1016/s0140-6736(01)05836-6.
citation: Senkal M, Zumtobel V, Bauer KH, Marpe B, Wolfram G, Frei A, Eickhoff U, Kemen M. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg. 1999 Dec;134(12):1309-16. doi: 10.1001/archsurg.134.12.1309.
citation: Braga M, Gianotti L, Radaelli G, Vignali A, Mari G, Gentilini O, Di Carlo V. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg. 1999 Apr;134(4):428-33. doi: 10.1001/archsurg.134.4.428.