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

Not Applicable

Not yet recruiting

• Conditions: Peritoneal Neoplasms; Intraoperative Care; Hyperthermic Intraperitoneal Chemotherapy; Fluid Therapy; Postoperative Complications
• Interventions: Other: Control; Other: Intra-operative albumin administration

• Registration Number: NCT06351475
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-04-02
• Study First Submitted QC: 2024-04-02
• Study First Posted: 2024-04-08
• Last Update Submitted: 2024-07-22
• Last Update Posted: 2024-07-23
• Study Start: 2024-09
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 146

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Control	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.
20% Albumin + Ringer Lactate group	Intra-operative albumin administration	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.

Primary Outcome Measures

Name	Time	Method
Comprehensive Complication Index score	At day 28	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

Secondary Outcome Measures

Name	Time	Method
Mortality	At day 28
Cumulative incidence of medical post operative complications	Up to day 28
Number of days alive out of intensive care unit	Up to day 28
Comprehensive Complication Index score	At day 7	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
Cumulative incidence of surgical post operative complications	Up to day 28
Need for mechanical ventilation	Up to day 28	Between surgery and day 28
Sequential organ failure assessment (SOFA) score variation	48 hours after surgery	Between pre operative period and 48h after surgery
Number of days alive out of hospital	Up to day 28
Volume of intra operative and post operative fluid therapy	48 hours after surgery
Need for renal replacement therapy	Up to day 28	Between surgery and day 28