The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients

NCT03277677 | Completed Phase 3 DMC

• 1 other identifier: IRB.113/60
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse pathophysiological effects in both animals and healthy human volunteers. Small randomized trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients. A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9% NaCl has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids. Major complications are the increased incidences of acute kidney injury and the need for renal replacement therapy, and that pathological hyperchloremia may increase postoperative mortality. Fluid resuscitation with 0.9% NaCl in animals with sepsis resulted in hyperchloremic metabolic acidosis, worsened AKI, and increased mortality when compared with resuscitation with a balanced crystalloid solution. Furthermore, hyperchloremic acidosis also resulted in increased concentrations of circulating inflammatory mediators in an experimental model of severe sepsis in rats, with a dose-dependent increase in circulating interleukin-6, tumor necrosis factor-a, and interleukin-10 concentrations with increasing acidosis. Thus, in this study, investigators compared the effects of a balanced crystalloid solution with 0.9% NaCl on the renal function in severe sepsis/septic shock patients. Investigators hypothesized that balanced crystalloid solution resuscitation would decrease AKI incidence and severity and would improve immunomodulatory effect when compared with 0.9% NaCl resuscitation.

Conditions

Sepsis; Septic Shock; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• The incidence of acute kidney injury for any stage and severity

  at day 7

Secondary Outcomes (9)

• The neutrophil function (chemotaxis, CD11b ) between two randomized groups at

  0, 24, and 72 hours after resuscitation.

• The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.

  at 0, 24, and 72 hours after resuscitation.

• The inflammatory marker (IL-6, IL-10) between two randomized groups at

  0, 24, and 72 hours after resuscitation.

• Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid

  at 0,24 and 72 hours after resuscitation.

• Urinary liver-type fatty acid binding protein (L-FABP)

  at 0,24 and 72 hours after resuscitation.

Study Arms (2)

normal saline

ACTIVE COMPARATOR

Drug: Normal saline

balanced solution

ACTIVE COMPARATOR

Drug: Ringer's Acetate

Interventions

Normal saline DRUG

for resuscitation in sepsis patients

normal saline

Ringer's Acetate DRUG

for resuscitation in sepsis patients

balanced solution

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Who need fluid resuscitation in the Emergency Room (ER).
• Who have fulfilled the criteria for sepsis/septic shock within the previous 24 hours according to sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
• o Patients with infection and resulted from a host's systemic inflammatory response syndrome (SIRS) to infection are defined as sepsis if meet the criteria 2 or more of
• Temperature \>38°C or \<36°C
• Heart rate \>90/min
• Respiratory rate \>20/min or PaCo2 \<32 mm Hg (4.3 kPa)
• White blood cell count \>12000/mm3 or \<4000/mm3 or \>10% immature bands.
• Patient who have Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.
• o Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level \>2 mmol/L (18 mg/dL) despite adequate volume resuscitation.
• AND where informed consent is obtainable either from the patient or by proxy (first degree relative, spouse) if patients aren't in fully conscious status (eg.comatose, drowsiness, irritable).

You may not qualify if:

• Patients with chronic kidney disease (CKD) defined by baseline serum creatinine \> 2.0 in male and 1.5 in female.
• Patients with End stage renal disease (ESRD) with or without renal replacement therapy.
• Patients with active cardiac disease : severe valvular heart, cardiomyopathy, decompensated heart failure NYHA II-IV, severe pulmonary hypertension.
• HIV/AIDs Patients.
• Allergy towards 0.9% NaCl or Ringer's Acetate.
• Any form of renal replacement therapy.
• Intracranial bleeding within current hospitalization.
• Therapy with corticosteroid or non steroidal anti-inflammatory substance.
• Patients who predicted not to survive more than 24 hours.
• Pregnant and lactating patients.
• Withdrawal of active therapy.

Sponsors & Collaborators

• Chulalongkorn University: lead

Study Sites (1)

Chulalongkorn university

Bangkok, 10330, Thailand

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic; Acute Kidney Injury

Interventions

Saline Solution; Ringer's acetate

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: July 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: March 1, 2021
• Last Updated: March 9, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)