Back to results

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

Primary Purpose

Sepsis, Septic Shock, Acute Kidney Injury

Status

Completed

Phase

Phase 3

Locations

Thailand

Study Type

Interventional

Intervention

Normal saline

Ringer's Acetate

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).

Exclusion criteria

Exclusion Criteria:

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.

Sites / Locations

Chulalongkorn university

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

normal saline

balanced solution

Arm Description

Outcomes

Primary Outcome Measures

The incidence of acute kidney injury for any stage and severity

Secondary Outcome Measures

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

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

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

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

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

Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.

Need of renal replacement therapy within 72 hours after randomization

Days alive without renal replacement therapy

Hospital length of stay for survivors sanctioned

Full Information

NCT ID

NCT03277677

First Posted

September 7, 2017

Last Updated

March 5, 2021

Sponsor

Chulalongkorn University

1. Study Identification

Unique Protocol Identification Number

NCT03277677

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

July 1, 2017 (Actual)

Primary Completion Date

July 1, 2018 (Actual)

Study Completion Date

March 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chulalongkorn University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sepsis, Septic Shock, Acute Kidney Injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

116 (Actual)

8. Arms, Groups, and Interventions

Arm Title

normal saline

Arm Type

Active Comparator

Arm Title

balanced solution

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Normal saline

Intervention Description

for resuscitation in sepsis patients

Intervention Type

Drug

Intervention Name(s)

Ringer's Acetate

Intervention Description

for resuscitation in sepsis patients

Primary Outcome Measure Information:

Title

The incidence of acute kidney injury for any stage and severity

Time Frame

at day 7

Secondary Outcome Measure Information:

Title

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

Time Frame

0, 24, and 72 hours after resuscitation.

Title

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

Time Frame

at 0, 24, and 72 hours after resuscitation.

Title

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

Time Frame

0, 24, and 72 hours after resuscitation.

Title

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

Time Frame

at 0,24 and 72 hours after resuscitation.

Title

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

Time Frame

at 0,24 and 72 hours after resuscitation.

Title

Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.

Time Frame

at 72 hours after randomization.

Title

Need of renal replacement therapy within 72 hours after randomization

Time Frame

within 72 hours after randomization

Title

Days alive without renal replacement therapy

Time Frame

in 28 days after randomization

Title

Hospital length of stay for survivors sanctioned

Time Frame

at 28 days after randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). Exclusion criteria Exclusion Criteria: 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.

Facility Information:

Facility Name

Chulalongkorn university

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs