Clinical trial NCT02502773: Fluid Loading in Abdominal Surgery: Saline Versus Hydroxyethyl Starch (FLASH Study)
Official title: Fluid Loading in Abdominal Surgery: Saline Versus Hydroxyethyl Starch: A Double-blinded Multicenter Prospective Randomized Trial (FLASH Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Morbidity
Postoperative Mortality
Keywords: Goal-directed therapy
Fluid loading
Abdominal surgery
Postoperative morbidity
Postoperative mortality
Individualized goal-directed fluid therapy
Elective or emergency abdominal surgery
General Anesthesia
Moderate-to-high risk surgical patients
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Agence Nationale de sécurité du Médicament
name: Programme Hospitalier de Recherche Clinique (AOI N° 2013 _ Futier)
name: Société Française Anesthesie-Réanimation (SFAR)
First posted: 2015-07-20
Enrollment: 826
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to evaluate whether the type of fluid (0.9% saline or 6% Hydroxyethyl starch 130/0.4) in the context of an individualized goal-directed fluid therapy is associated with a difference in morbidity and mortality within the first 14 days in patients at moderate-to-high risk of postoperative complications after abdominal surgery.

Detailed description: Fluid administration is the mainstay treatment for suspected hypovolemia during surgery, but the effects of different crystalloid and colloid solutions on outcome remain poorly explored in surgical patients.

Two recent international multicenter studies (6S and CHEST studies) have shown that, compared to crystalloid solutions, the use of hydroxyethyl starch (HES) could be responsible for higher morbidity, especially renal failure, and mortality in ICU patients, thus leading to a recent restriction of their range of indications.

In contrast, in surgical patients, recent meta-analyses have concluded on the absence of difference in terms of mortality and postoperative renal failure between crystalloids and latest generation HES. Excessive fluid administration during surgery is associated with increased risk of postoperative morbidity, including renal dysfunction and mortality. It has been suggested that, compared with the volume-restoring effects of colloids, crystalloid use may require the administration of higher fluid volumes, which may contribute to poorer outcomes. In the surgical context, clinical trials and meta-analyses have shown that individualized goal-direct fluid administration can reduce postoperative morbidity. Although most GDT studies have used colloid solutions for fluid loading, the effects of the type of fluids are currently unknown and crystalloids are proposed for first-line therapy.

The proposed Flash multicenter study will be conducted to assess if the use of HES or crystalloid solutions during an individualized GDT contribute to outcome differences in patients at moderate-to-high risk of postoperative complications after abdominal surgery. As these fluids are widely used during surgery and because of current concerns about the risks related to the use of HES-based products in ICU patients, the trial will provide important data to clinicians involved in perioperative care.

Eligibility criteria: Inclusion Criteria:

All adult patients who

* Undergo elective or emergency abdominal surgery under general anesthesia
* With an estimated surgical duration greater than or equal to 2 hours
* With moderate-to-high risk of postoperative complications defined by an AKI risk index≥ class 3, as defined by the presence of at least 4 of the following factors: age\> 56 years, male gender, intraperitoneal surgery, active congestive heart failure, ascites, hypertension, emergency surgery, mild or moderate renal insufficiency, diabetes mellitus treated by oral or insulin therapy

Exclusion Criteria:

The following patients will not be evaluated for inclusion:

* Age \<18 years
* Preoperative acute heart failure
* Preoperative acute coronary insufficiency
* Preoperative severe renal failure (defined by creatinine clearance \<30 ml/min or requiring renal replacement therapy)
* Preoperative shock defined by the need for vasoactive amines
* History of allergy with the use of 6% Hydroxethyl starch 130/0.4
* Contraindication to the use of HES: sepsis, burnt patient, renal insufficiency or dialysis, cerebral hemorrhage, ICU patient , hypervolemia, lung edema, dehydration, severe hypernatremia or severe hyperchloremia, severe hepatic insufficiency, congestive heart failure, severe coagulopathy, organ transplant
* Patient's or relative's refusal to participate
* Parturient or breastfeeding woman
* Protected major (guardianship)

Primary outcomes:
measure: Renal dysfunction
timeFrame: during the first 14 postoperative days
measure: Pulmonary complication
timeFrame: during the first 14 postoperative days
measure: Cardiovascular complication
timeFrame: during the first 14 postoperative days
measure: Infectious complication
timeFrame: during the first 14 postoperative days
measure: Surgical complication
timeFrame: during the first 14 postoperative days
Secondary outcomes:
measure: Total fluid volume
timeFrame: during the surgical period and the first 24 postoperative hours
measure: Volume of blood loss
timeFrame: during the surgical period and the first 24 postoperative hours
measure: Renal complications : oliguria
timeFrame: within 14 days
measure: Cardiovascular complications
timeFrame: within 14 days
measure: Respiratory complications
timeFrame: within 14 days
measure: SIRS score
timeFrame: within 14 days
measure: Infectious complications
timeFrame: within 14 days
measure: Surgical complications
timeFrame: within 14 days
measure: Severity organ failure assessment score from postoperative
timeFrame: Day-1 to Day-7
measure: Unexpected ICU admission (or readmission) following surgery
timeFrame: within 28 days
measure: All-cause mortality
timeFrame: 28 days
measure: All-cause mortality
timeFrame: 3 months
measure: Serum lactate
timeFrame: from Day-1 to Day-7
measure: C-reactive protein
timeFrame: from Day-1 to Day-7
measure: Plasma chloride
timeFrame: from Day-1 to Day-7
measure: number of units of packed red blood cells
timeFrame: during the surgical period and the first 24 postoperative hours
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Emmanuel FUTIER
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Clermont-Ferrand
name: Jean-Etienne BAZIN
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Montpellier
name: Samir JABER
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU Strasbourg
name: Julien POTTECHER
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux
name: Alexandre OUATTARA
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint-Antoine (APHP)
name: Thomas LESCOT
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Rennes
name: Hélène BELOEIL
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU LILLE
name: Gilles LEBUFFE
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Nîmes
name: Philippe CUVILLON
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Tenon (APHP)
name: Julien BUREY
role: PRINCIPAL_INVESTIGATOR
affiliation: CH ORLEANS
name: Willy-Serge MFAM
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospices Civils de Lyon
name: Vincent PIRIOU
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HM
name: Marc LEONE
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Nîmes
name: Sébastien BERTRAN
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Paoli-Calmettes
name: Marion FAUCHER
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Beaujon
name: Catherine PAUGAM-BURTZ
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HM
name: Lionel VELLY
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Brest
name: Olivier HUET
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Angers
name: Sigismond LASOCKI
role: PRINCIPAL_INVESTIGATOR
affiliation: CH VALENCIENNES
name: Pierre SAINT-LEGER
role: PRINCIPAL_INVESTIGATOR
References:
citation: Futier E, Garot M, Godet T, Biais M, Verzilli D, Ouattara A, Huet O, Lescot T, Lebuffe G, Dewitte A, Cadic A, Restoux A, Asehnoune K, Paugam-Burtz C, Cuvillon P, Faucher M, Vaisse C, El Amine Y, Beloeil H, Leone M, Noll E, Piriou V, Lasocki S, Bazin JE, Pereira B, Jaber S; FLASH Trial Group; Lasocki S, Huet O, Cadic A, Jacob C, Paugam-Burtz C, Restoux A, Ouattara A, Feitita I, Deloge E, Defaye M, Joannes-Boyau O, Carles P, Napolitano G, Monziols S, Futier E, Vignaud M, Paul S, Gahbiche K, Fayon J, Laroche E, Bazin JE, Brandely A, Le Moal C, Lebuffe G, Garot M, Piriou V, Jaber S, Chanques G, Verzilli D, De Jong A, Millot A, Castagnoli A, Leone M, Pastene B, Castelli C, Medam S, Velly L, Vaisse C, Faucher M, Asehnoune K, Samba E, Roquilly A, Le Penndu M, Cuvillon P, Yves Lefrant J, Wira O, Dubout E, Mfam WS, Lescot T, Begneu E, Burey J, Cirilovic T, Beloeil H, Allo G, Pottecher J, Lebas B, Venot C, Rameau JP, Dimache F, Leger PS, El Amine Y. Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial. JAMA. 2020 Jan 21;323(3):225-236. doi: 10.1001/jama.2019.20833.
citation: Futier E, Biais M, Godet T, Bernard L, Rolhion C, Bourdier J, Morand D, Pereira B, Jaber S; FLASH trial management committee. Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial. Trials. 2015 Dec 21;16:582. doi: 10.1186/s13063-015-1085-3.