Clinical trial NCT06351475: Efficacy of Intraoperative Use of 20% Albumin Combined With Ringer Lactate Versus Ringer Lactate During Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Peritoneal Neoplasms
Hyperthermic Intraperitoneal Chemotherapy
Intraoperative Care
Fluid Therapy
Postoperative Complications
Keywords: Cytoreductive surgery
Hyperthermic intraperitoneal chemotherapy
Albumin administration
Fluid therapy
Post operative prognosis
Randomized clinical trial
Open label clinical trial
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-04-08
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Comprehensive Complication Index score
timeFrame: At day 28
Secondary outcomes:
measure: Mortality
timeFrame: At day 28
measure: Comprehensive Complication Index score
timeFrame: At day 7
measure: Volume of intra operative and post operative fluid therapy
timeFrame: 48 hours after surgery
measure: Cumulative incidence of surgical post operative complications
timeFrame: Up to day 28
measure: Cumulative incidence of medical post operative complications
timeFrame: Up to day 28
measure: Need for mechanical ventilation
timeFrame: Up to day 28
measure: Need for renal replacement therapy
timeFrame: Up to day 28
measure: Sequential organ failure assessment (SOFA) score variation
timeFrame: 48 hours after surgery
measure: Number of days alive out of intensive care unit
timeFrame: Up to day 28
measure: Number of days alive out of hospital
timeFrame: Up to day 28
Other outcomes:
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