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

Официальное название

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

Обзор

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.

Вмешательства

• Другое 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 en
• Другое Control
  Ringer lactate

Первичные конечные точки

• Comprehensive Complication Index score [Срок оценки: At day 28]

Вторичные конечные точки (12)

• Comprehensive Complication Index score [Срок оценки: At day 7]
• Volume of intra operative and post operative fluid therapy [Срок оценки: 48 hours after surgery]
• Cumulative incidence of surgical post operative complications [Срок оценки: Up to day 28]
• Incidence of infectious complications [Срок оценки: Up to day 28]
• Number of days under mechanical ventilation outside the operating room [Срок оценки: Up to day 28]
• Number of days under renal replacement therapy [Срок оценки: Up to day 28]
• Sequential organ failure assessment (SOFA) score variation [Срок оценки: 48 hours after surgery]
• Number of days alive out of intensive care unit [Срок оценки: Up to day 28]
• Number of days alive out of hospital [Срок оценки: Up to day 28]
• Incidence of medical complications [Срок оценки: Up to day 28]
• Cumulative incidence of death in intensive care unit [Срок оценки: Up to day 28]
• Cumulative incidence of death in hospital [Срок оценки: Up to day 28]

Критерии участия

Критерии включения

• 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

Критерии исключения

• Adults >75 years old
• Functional status rendering the patient ineligible for cytoreduction with CHIP (ECOG > 2 or Karnofsky index < 75)
• Pre-existing preoperative conditions affecting albuminemia (hepatic cirrhosis, nephrotic syndrome, exudative enteropathy, malnutrition)
• Severe preoperative hypoalbuminemia (albuminemia < 20 g/L)
• History of chronic left heart failure with reduced left ventricular ejection fraction (left ventricular ejection fraction < 40%)
• Patients at high risk of perioperative and postoperative pulmonary complications (atelectasis, significant pleural effusions)
• Significant ascites with preoperative respiratory repercussions
• Uncontrolled diabetes (HbA1c > 8.5%)
• Allergy to exogenous human albumin and its excipients.
• Contraindication to the administration of Ringer's lactate (history of allergy)
• Hyperkalemia > 6.0 mmol/L
• Hypercalcemia (total calcium > 2.60 mmol/L)
• Chronic use of digitalis and hyperkalemic diuretics
• Pregnancy, breastfeeding
• Known preoperative renal failure (GFR < 30 mL/min/1.73m2 or extrarenal purification)
• Recent brain trauma < 6 months (traumatic, ischemic, or hemorrhagic)
• Participation in another interventional study involving human subjects or being in the exclusion period following a previous study involving human subjects, if applicable
• Patient deprived of liberty
• Patient under guardianship or curatorship

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Франция · 7 центров

• Institut régional du Cancer de Montpellier — Montpellier
• La Pitié Salpetriere hospital — Paris
• Lariboisière hospital — Paris
• Saint Louis hospital — Paris
• Robert Debré hospital — Reims
• Hôpital Hautepierre / UIC ARMO — Strasbourg
• Gustave Roussy Institute — Villejuif

Публикации

• Deniau B, Moreau A, Monsel A, Faitot V, Pottecher J, Zoric L, Suria S, Bankole E, Michelet D, Poirier N, Plaud B, Chaix C, Biard L, Depret F. Efficacy of intraoperative use of 20% albumin in combination with Ringer's lactate versus Ringer's lactate during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: protocol for a randomised controlled, open-label clinical trial (ALBUCHIP PMID 42044958

Идентификаторы

NCT: NCT06351475 · APHP230864

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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