Fluid Loading in Abdominal Surgery: Saline Versus Hydroxyethyl Starch (FLASH Study)

NCT ID: NCT02502773

Last Updated: 2019-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 826 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2018-10-22

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.

Conditions

Postoperative Morbidity; Postoperative Mortality

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

crystalloid group

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

Group Type: EXPERIMENTAL

Hydroxethyl starch

Intervention Type: DRUG

colloid group

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

Group Type: EXPERIMENTAL

Hydroxethyl starch

Intervention Type: DRUG

Interventions

Hydroxethyl starch

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agence Nationale de sécurité du Médicament

OTHER

Sponsor Role: collaborator

Programme Hospitalier de Recherche Clinique (AOI N° 2013 _ Futier)

UNKNOWN

Sponsor Role: collaborator

Société Française Anesthesie-Réanimation (SFAR)

UNKNOWN

Sponsor Role: collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel FUTIER

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Jean-Etienne BAZIN

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Samir JABER

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Julien POTTECHER

Role: PRINCIPAL_INVESTIGATOR

CHRU Strasbourg

Alexandre OUATTARA

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Thomas LESCOT

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint-Antoine (APHP)

Hélène BELOEIL

Role: PRINCIPAL_INVESTIGATOR

CHU Rennes

Gilles LEBUFFE

Role: PRINCIPAL_INVESTIGATOR

CHRU LILLE

Philippe CUVILLON

Role: PRINCIPAL_INVESTIGATOR

CHU Nîmes

Julien BUREY

Role: PRINCIPAL_INVESTIGATOR

Hôpital Tenon (APHP)

Willy-Serge MFAM

Role: PRINCIPAL_INVESTIGATOR

CH ORLEANS

Vincent PIRIOU

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Marc LEONE

Role: PRINCIPAL_INVESTIGATOR

AP-HM

Sébastien BERTRAN

Role: PRINCIPAL_INVESTIGATOR

CHU Nîmes

Marion FAUCHER

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Catherine PAUGAM-BURTZ

Role: PRINCIPAL_INVESTIGATOR

Hôpital Beaujon

Lionel VELLY

Role: PRINCIPAL_INVESTIGATOR

AP-HM

Olivier HUET

Role: PRINCIPAL_INVESTIGATOR

CHU Brest

Sigismond LASOCKI

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Angers

Pierre SAINT-LEGER

Role: PRINCIPAL_INVESTIGATOR

CH VALENCIENNES

Locations

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 31961418 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26690683 (View on PubMed)

Other Identifiers

2014-005575-84

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHU-0242

Identifier Type: -

Identifier Source: org_study_id