Acetated Ringer's Solution Versus Saline in Patients With Septic Shock

The primary aim of this trial is to compare the effect of acetated ringer's solution with that of saline for therapy on the incidence and development of major adverse renal events among septic shock patients. The investigators hypothesize that use of acetated ringer's solution for resuscitation among septic shock patients will reduce the incidence of major adverse kidney events.

Study Overview

• Status: Not yet recruiting
• Conditions: Septic Shock Hyperdynamic
• Intervention / Treatment: Drug: Fluid resuscitation

Detailed Description

Normal saline and Ringer's solutions are the preferred crystalloid fluids administered in early septic shock. However, evidence have associated saline with hyperchloremia and secondary metabolic acidosis, and renal vasoconstriction, increased incidence of acute kidney injury (AKI) and mortality. The primary aim of this trial is to compare the effect of acetated ringer's solution with that of saline for therapy on the incidence and development of major adverse renal events among septic shock patients. The investigators hypothesize that use of acetated ringer's solution for resuscitation among septic shock patients will reduce the incidence of major adverse kidney events.

• Study Type: Interventional
• Enrollment (Anticipated): 2000
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult patients presenting to the ICU diagnosed as septic shock within 24 hours.

Exclusion Criteria:

1. Pregnancy;
2. Likely requirement for immediate hemodialysis or renal replacement therapy;
3. Patients have already received fluids for more than 4 liters;
4. Patient in extremis or death deemed imminent and inevitable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: saline group; Use saline for fluid resuscitation during the first 72 hours after enrollment	Drug: Fluid resuscitation; Use the choice of crystalloid for resuscitation during the first 72 hours after enrollment
Experimental: Acetated Ringer's solution group; Use acetated Ringer's solution for fluid resuscitation during the first 72 hours after enrollment	Drug: Fluid resuscitation; Use the choice of crystalloid for resuscitation during the first 72 hours after enrollment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major adverse renal events in 28 days	Incidence of major adverse renal events	28 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of kidney injury	Incidence of kidney injury	28 day
Serum creatinine（umol/L）	serum creatinine（umol/L）	28 day

Collaborators and Investigators

• Sponsor: Southeast University, China

Publications and helpful links

General Publications

• Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637.
• Peters E, Antonelli M, Wittebole X, Nanchal R, Francois B, Sakr Y, Vincent JL, Pickkers P. A worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from The Intensive Care Over Nations audit. Crit Care. 2018 Aug 3;22(1):188. doi: 10.1186/s13054-018-2112-z.
• Yunos NM, Kim IB, Bellomo R, Bailey M, Ho L, Story D, Gutteridge GA, Hart GK. The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med. 2011 Nov;39(11):2419-24. doi: 10.1097/CCM.0b013e31822571e5.
• Suetrong B, Pisitsak C, Boyd JH, Russell JA, Walley KR. Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients. Crit Care. 2016 Oct 6;20(1):315. doi: 10.1186/s13054-016-1499-7.
• Raghunathan K, Shaw A, Nathanson B, Sturmer T, Brookhart A, Stefan MS, Setoguchi S, Beadles C, Lindenauer PK. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med. 2014 Jul;42(7):1585-91. doi: 10.1097/CCM.0000000000000305.
• Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012 Oct 17;308(15):1566-72. doi: 10.1001/jama.2012.13356.
• Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 2, 2020
• First Submitted That Met QC Criteria: August 9, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Crystalloid; Renal failure; Renal dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 2018ZDSYLL105-P01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No