Efficacy of Intraoperative Use of 20% Albumin Combined With Ringer Lactate Versus Ringer Lactate During Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy

Postoperative Complications Clinical Trial

— ALBUCHIP  

Official title:

Evaluation de l'efficacité du Remplissage Vasculaire Par de l'ALBUmine Humaine 20% + Ringer Lactate comparé au Ringer Lactate Seul Chez Les Patients opérés Par cytoréduction Avec CHimiothérapie Intrapéritonéale hyPerthermique

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06351475
• Other study ID #: APHP230864
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2024
• Est. completion date: October 2026

Study information

• Verified date: March 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Delphine CHERON-LEROY, Dr
• Phone: +33142499394
• Email: delphinecheron[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as the standard of care for the treatment of peritoneal metastases. Cytoreductive surgery with HIPEC is characterized by large intra operative fluid shift secondary to surgical resection, peritoneal inflammation and capillary shifts, requesting high volume of intra operative fluid therapy. Previous studies found a strong association between intra operative hypovolemia or volume overload with post operative outcomes. Albumin as an intravenous fluid has been widely studied in critical ill patients, but evaluation of its efficacy during major surgery on post operative clinical outcomes are lacking. We hypothesize that a reduction of intra operative crystalloid volume infusion by using 20% albumin during CRS with HIPEC could improve patients' prognosis. The aim of this study will be to assess the efficacy of 20% albumin combined with Ringer Lactate versus Ringer Lactate for fluid therapy during CRS with HIPEC on post operative outcome at 28 day.

Methods and analysis The study protocol has been designed and written in accordance with the Prospective randomised, comparative, controlled, prospective, open-label, with parallel group and multicentre clinical trial.

Recruitment, randomisation and allocation Information on the study and screening of patients will be conducted during the consultation of anaesthesia (= selection visit), 2 months at 3 days before the surgery. Information notice and consent form will be delivered. The day before the surgery, anaesthesiologist who will conduct the pre anaesthetic visit will be able to include patients in the study (=inclusion visit). Randomisation will be done at the inclusion visit after information and signature of consent form of voluntary patients. A randomization number will be assigned. The 1:1 randomisation will be centralized via an online interface ensuring secret group assignment, and based on predefined randomisation lists with variable-size permutation blocks, stratified by center. Randomisation will be accomplished using a computer-generated random sequence.

Randomized Open, Blinded endpoint (PROBE) design. This study is a randomised, comparative, controlled, prospective, open-label, with parallel group and multicentre clinical trial.

Intervention

• 20% Albumin + Ringer Lactate group (intervention group) Per-operative fluid therapy consisting in Ringer Lactate combined with 20% albumin. Patients will receive a bolus of 3 mL/kg on one hour of 20% albumin from anaesthetic induction. Then, infusion of 20% albumin (100 mL, 20g) will be administered for each 1200 mL of vascular filling by Ringer Lactate. Dosage of intra operative albuminemia will be realized 2 hours after the end of the bolus or infusion to ensure albuminemia is within the target concentrations (35-45 g/L). Use of 20% albumin will be realized for the entire duration of the surgery and stopped at the end of the surgery.

• Control group Ringer Lactate for intra operative fluid management based on the latest scientific recommendations. As the the study is an open labelled randomized clinical trial, placebo use is not planned.

Outcome measures The primary outcome will be the Comprehensive Complication Index (CCI score) at day 28 after CRS with HIPEC. Secondary outcomes are mortality at day 28, CCI score at day 7, volume of intra operative and post operative (48h) post operative fluid therapy, cumulated incidence of surgical post operative complications, cumulated incidence of medical post operative complications, need for mechanical ventilation, renal replacement therapy between surgery and day 28, SOFA score variation between pre operative period and 48h after surgery, number of days alive out of intensive care unit and out of hospital until day 28

Sample size calculation To ensure a power of 80%, a number of patients 130 (65 patients by group) will be necessary with a reduction of 13.6 (SD 24) points of the CCI score at day 28 in the intervention group. Because of a risk of neoplastic evolution between anaesthetic consultation and randomisation (10% of early cancellation), a total of 146 patients (73 by group) will be included in the study.

Discussion In summary, ALBUCHIP study will be the first randomized clinical trial assessing efficacy of intraoperative use of 20% albumin combined with Ringer Lactate versus Ringer Lactate during CRS with HIPEC. Results yielded from this study will be helpful for vascular filling during CRS with HIPEC but, thanks to ancillary studies, to improve pathophysiological understanding of this surgery.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 146
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male and female patients aged 18 years old and older

• Planned cytoreductive surgery with HIPEC for peritoneal carcinomatosis (from gynaecological or digestive origin)

• Patient volunteer for the study and provided written informed consent

• Patient affiliated to the French Health Insurance

Exclusion Criteria:

• Refusal to participate to the study

• Pre operative disease influencing plasmatic albumin levels (hepatic cirrhosis, nephrotic syndrome, exudative enteropathy, severe denutrition with albuminemia < 20g/L)

• Chronic heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%)

• Allergy to exogen human albumin

• Pregnancy

• Breast feeding

• Chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73m2 or need for renal replacement therapy)

Related Conditions & MeSH terms

• Fever
• Fluid Therapy
• Hyperthermia
• Hyperthermic Intraperitoneal Chemotherapy
• Intraoperative Care
• Peritoneal Neoplasms
• Postoperative Complications

Intervention

Other:
• Intra-operative albumin administration
Patients randomized in the intervention group (20% albumin + Ringer Lactate) will receive, during cytoreductive surgery with HIPEC, fluid therapy consisting in Ringer Lactate (based on a fluid management protocol specifically set up for the study, and based on latest recommendations) combined with 20% albumin. Patients randomized in the intervention group will receive a bolus of 3 mL/kg on one hour of 20% albumin from anesthetic induction . Dosage of albuminemia will be done 2 hours after the end of the bolus (target of 35-45 g/L of intra operative albuminemia). Then, infusion of 20% albumin (100 mL, 20g) will be administered for each 1200 mL of vascular filling by Ringer Lactate. Dosage of intra operative albuminemia will be realized 2 hours after the end of the bolus or infusion to ensure albuminemia is within the target concentrations (35-45 g/L). Use of 20% albumin will be realized for the entire duration of the surgery and stopped at the end of the surgery.
• Control
Ringer lactate

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comprehensive Complication Index score	The Comprehensive Complication Index (CCI) is a score ranging from 0 to 100, calculated using all complications and their treatment after abdominal surgery.; The CCI is that it is a linear scale ranging from 0 to 100, where 100 represents death	At day 28
Secondary	Mortality		At day 28
Secondary	Comprehensive Complication Index score	The Comprehensive Complication Index (CCI) is a score ranging from 0 to 100, calculated using all complications and their treatment after abdominal surgery.; The CCI is that it is a linear scale ranging from 0 to 100, where 100 represents death	At day 7
Secondary	Volume of intra operative and post operative fluid therapy		48 hours after surgery
Secondary	Cumulative incidence of surgical post operative complications		Up to day 28
Secondary	Cumulative incidence of medical post operative complications		Up to day 28
Secondary	Need for mechanical ventilation	Between surgery and day 28	Up to day 28
Secondary	Need for renal replacement therapy	Between surgery and day 28	Up to day 28
Secondary	Sequential organ failure assessment (SOFA) score variation	Between pre operative period and 48h after surgery	48 hours after surgery
Secondary	Number of days alive out of intensive care unit		Up to day 28
Secondary	Number of days alive out of hospital		Up to day 28