Clinical trial NCT04356859: The Acute Burn ResUscitation Multicenter Prospective Trial
Official title: The Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Burn Injury
Keywords: Resuscitation
Lead sponsor: American Burn Association
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2020-04-22
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will be based on "intent to treat." Consecutively admitted and eligible burn patients will be assigned to one of two treatment groups (Colloid or Crystalloid) within 12 hours of burn injury.
Primary purpose: TREATMENT

Brief summary: This is a prospective randomized multi-center study which will compare acute fluid resuscitation using a colloid strategy (LR + 5% Albumin) to a crystalloid strategy (LR alone), in adults with an acute burn involving at least 25% of their total body surface area.

Detailed description: Enrolled subjects will be randomly assigned to either the Colloid Group or the Crystalloid Group. Randomization will be based on an intent-to-treat basis. In order to ensure that the two groups have comparable injury severity at baseline, randomization will be block- stratified based on age (18-50 and \> 50 years), burn size (25-50% and \> 50% TBSA), and presence of inhalation injury confirmed by bronchoscopy (present or absent). In the Colloid Group resuscitation starts with LR and then 5% albumin will be introduced between 8 and 12 hours post burn in a ratio of 1/3 albumin to 2/3 LR. In the Crystalloid Group resuscitation is with LR only. Each group will have their study fluid maintained for the 1st 48 hours post burn and study fluids in each group will be identically titrated to the urinary output.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Total burn size (second and third degree) is ≥ 25% of the TBSA
* Burn center admission within 12 hours of injury.
* There is a plan for formal fluid resuscitation.

Exclusion Criteria:

* Significant associated trauma
* High voltage (≥ 1000 volts) electrical burns
* Burn wound excision surgery within 48 hours from injury
* Fresh frozen plasma (FFP) given at any time ≤ 48 hours from injury
* Hypertonic saline (HTS) given at any time ≤ 48 hours from injury
* Hydroxyethyl starch (HES) given at any time ≤ 48 hours from injury
* High dose Vitamin C infusion given at any time ≤ 48 hours from injury
* Administration of human albumin prior to randomization
* Palliative comfort measures are instituted ≤ 48 hours from injury
* Pregnancy
* Pre-injury chronic renal insufficiency equal to or greater than stage 3
* Pre-injury chronic hepatic disease (Child-Pugh B or C)
* Pre-injury left ventricular (LV) dysfunction (echocardiography LV grade II-IV or ejection fraction ≤ 35%)

Primary outcomes:
measure: Volume of fluid received during resuscitation for burn injury
timeFrame: 24 hours post burn injury
Secondary outcomes:
measure: Volume of fluid received during resuscitation for burn injury
timeFrame: 48 hours post burn injury
measure: Urine output during resuscitation for burn injury
timeFrame: 24 and 48 hours post burn injury
measure: Number of crossovers
timeFrame: 48 hours post burn injury
measure: Peak lactate and delta lactate
timeFrame: 48 hours post burn injury
measure: Peak intra-abdominal pressure (IAP) and delta IAP
timeFrame: 48 hours post burn injury
measure: Occurrence of Abdominal compartment syndrome
timeFrame: 48 hours post burn injury
measure: Occurrence of Limb or abdominal fasciotomy
timeFrame: 48 hours post burn injury
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: 48, 72, and 96 hours post burn injury
measure: Acute kidney injury (AKI)
timeFrame: 96 hours post burn injury
measure: Duration of intubation/mechanical ventilation
timeFrame: 96 hours post burn injury
measure: PaO2/FiO2 ratios
timeFrame: 24, 48, 72, and 96 hours post burn injury
measure: Time to wound healing
timeFrame: 7 days post last surgery for grafting of burn injury
measure: Survival
timeFrame: 28 days post injury and hospital discharge
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Burn Center Valleywise Health
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis, Regional Burn Center
state: California
city: Torrance
country: United States
facility: Torrance Memorial
state: California
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Maywood
country: United States
facility: Loyola Medicine
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Healthcare
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Health System
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi St. Francis
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin Healthcare
state: Minnesota
city: Livingston
country: United States
facility: Cooperman Barnabas Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center Health Network
state: New York
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: Metrohealth Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Health
state: Oregon
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: The University of Tennessee Health Science Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Seattle
country: United States
facility: Regional Burn Center at Harborview
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Health
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: UC Davis Health
name: David G Greenhalgh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pruitt BA Jr. Protection from excessive resuscitation: "pushing the pendulum back". J Trauma. 2000 Sep;49(3):567-8. doi: 10.1097/00005373-200009000-00030. No abstract available.
citation: Zak AL, Harrington DT, Barillo DJ, Lawlor DF, Shirani KZ, Goodwin CW. Acute respiratory failure that complicates the resuscitation of pediatric patients with scald injuries. J Burn Care Rehabil. 1999 Sep-Oct;20(5):391-9. doi: 10.1097/00004630-199909000-00011.
citation: Hobson KG, Young KM, Ciraulo A, Palmieri TL, Greenhalgh DG. Release of abdominal compartment syndrome improves survival in patients with burn injury. J Trauma. 2002 Dec;53(6):1129-33; discussion 1133-4. doi: 10.1097/00005373-200212000-00016.
citation: Klein MB, Hayden D, Elson C, Nathens AB, Gamelli RL, Gibran NS, Herndon DN, Arnoldo B, Silver G, Schoenfeld D, Tompkins RG. The association between fluid administration and outcome following major burn: a multicenter study. Ann Surg. 2007 Apr;245(4):622-8. doi: 10.1097/01.sla.0000252572.50684.49.
citation: Recinos PR, Hartford CA, Ziffren SE. Fluid resuscitation of burn patients comparing a crystalloid with a colloid containing solution: a prospective study. J Iowa Med Soc. 1975 Oct;65(10):426-32. No abstract available.
citation: Goodwin CW, Dorethy J, Lam V, Pruitt BA Jr. Randomized trial of efficacy of crystalloid and colloid resuscitation on hemodynamic response and lung water following thermal injury. Ann Surg. 1983 May;197(5):520-31. doi: 10.1097/00000658-198305000-00004.
citation: Cooper AB, Cohn SM, Zhang HS, Hanna K, Stewart TE, Slutsky AS; ALBUR Investigators. Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score. Transfusion. 2006 Jan;46(1):80-9. doi: 10.1111/j.1537-2995.2005.00667.x.
citation: O'Mara MS, Slater H, Goldfarb IW, Caushaj PF. A prospective, randomized evaluation of intra-abdominal pressures with crystalloid and colloid resuscitation in burn patients. J Trauma. 2005 May;58(5):1011-8. doi: 10.1097/01.ta.0000162732.39083.15.
citation: Muller Dittrich MH, Brunow de Carvalho W, Lopes Lavado E. Evaluation of the "Early" Use of Albumin in Children with Extensive Burns: A Randomized Controlled Trial. Pediatr Crit Care Med. 2016 Jun;17(6):e280-6. doi: 10.1097/PCC.0000000000000728.
citation: Cartotto R, Callum J. A review of the use of human albumin in burn patients. J Burn Care Res. 2012 Nov-Dec;33(6):702-17. doi: 10.1097/BCR.0b013e31825b1cf6.
citation: Baxter CR, Shires T. Physiological response to crystalloid resuscitation of severe burns. Ann N Y Acad Sci. 1968 Aug 14;150(3):874-94. doi: 10.1111/j.1749-6632.1968.tb14738.x. No abstract available.
citation: Pruitt BA Jr. Fluid and electrolyte replacement in the burned patient. Surg Clin North Am. 1978 Dec;58(6):1291-1312. doi: 10.1016/s0039-6109(16)41692-0. No abstract available.
citation: Pruitt BA Jr. The burn patient: II. Later care and complications of thermal injury. Curr Probl Surg. 1979 May;16(5):1-95. doi: 10.1016/s0011-3840(79)80009-x.
citation: Cartotto RC, Innes M, Musgrave MA, Gomez M, Cooper AB. How well does the Parkland formula estimate actual fluid resuscitation volumes? J Burn Care Rehabil. 2002 Jul-Aug;23(4):258-65. doi: 10.1097/00004630-200207000-00006.
citation: Cartotto R, Zhou A. Fluid creep: the pendulum hasn't swung back yet! J Burn Care Res. 2010 Jul-Aug;31(4):551-8. doi: 10.1097/BCR.0b013e3181e4d732.
citation: Engrav LH, Colescott PL, Kemalyan N, Heimbach DM, Gibran NS, Solem LD, Dimick AR, Gamelli RL, Lentz CW. A biopsy of the use of the Baxter formula to resuscitate burns or do we do it like Charlie did it? J Burn Care Rehabil. 2000 Mar-Apr;21(2):91-5. doi: 10.1097/00004630-200021020-00002.
citation: Cancio LC, Chavez S, Alvarado-Ortega M, Barillo DJ, Walker SC, McManus AT, Goodwin CW. Predicting increased fluid requirements during the resuscitation of thermally injured patients. J Trauma. 2004 Feb;56(2):404-13; discussion 413-4. doi: 10.1097/01.TA.0000075341.43956.E4.
citation: Saffle JI. The phenomenon of "fluid creep" in acute burn resuscitation. J Burn Care Res. 2007 May-Jun;28(3):382-95. doi: 10.1097/BCR.0B013E318053D3A1.
citation: Jelenko C 3rd, Williams JB, Wheeler ML, Callaway BD, Fackler VK, Albers CA, Barger AA. Studies in shock and resuscitation, I: use of a hypertonic, albumin-containing, fluid demand regimen (HALFD) in resuscitation. Crit Care Med. 1979 Apr;7(4):157-67.
citation: Lawrence A, Faraklas I, Watkins H, Allen A, Cochran A, Morris S, Saffle J. Colloid administration normalizes resuscitation ratio and ameliorates "fluid creep". J Burn Care Res. 2010 Jan-Feb;31(1):40-7. doi: 10.1097/BCR.0b013e3181cb8c72.
citation: Faraklas I, Lam U, Cochran A, Stoddard G, Saffle J. Colloid normalizes resuscitation ratio in pediatric burns. J Burn Care Res. 2011 Jan-Feb;32(1):91-7. doi: 10.1097/BCR.0b013e318204b379.
citation: Mehrkens HH, Ahnefeld FW. Volume and fluid replacement in the early post burn period: an animal experimental study. Burns 1979;5:113-15
citation: Asch MJ, Feldman RJ, Walker HL, Foley FD, Popp RL, Mason AD Jr, Pruitt BA Jr. Systemic and pulmonary hemodynamic changes accompanying thermal injury. Ann Surg. 1973 Aug;178(2):218-21. doi: 10.1097/00000658-197308000-00020. No abstract available.
citation: Demling RH, Kramer G, Harms B. Role of thermal injury-induced hypoproteinemia on fluid flux and protein permeability in burned and nonburned tissue. Surgery. 1984 Feb;95(2):136-44.
citation: Demling RH, Kramer GC, Gunther R, Nerlich M. Effect of nonprotein colloid on postburn edema formation in soft tissues and lung. Surgery. 1984 May;95(5):593-602.
citation: Onarheim H, Reed RK. Thermal skin injury: effect of fluid therapy on the transcapillary colloid osmotic gradient. J Surg Res. 1991 Mar;50(3):272-8. doi: 10.1016/0022-4804(91)90190-w.
citation: Moncrief JA. Effect of various fluid regimens and pharmacologic agents on the circulatory hemodynamics of the immediate postburn period. Ann Surg. 1966 Oct;164(4):723-52. doi: 10.1097/00000658-196610000-00017. No abstract available.
citation: Park SH, Hemmila MR, Wahl WL. Early albumin use improves mortality in difficult to resuscitate burn patients. J Trauma Acute Care Surg. 2012 Nov;73(5):1294-7. doi: 10.1097/TA.0b013e31827019b1.