Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: A Pilot Feasibility Study

NCT03340805 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-013936
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this pilot study is to assess overall feasibility prior to embarking on a larger randomized pragmatic trial comparing the clinical effectiveness of fluid resuscitation with NS versus LR for pediatric patients with suspected septic shock. Necessary feasibility assessments include ensuring appropriate compliance with study fluid in each of the two arms, effectiveness of study enrollment using a pragmatic study design embedded within routine clinical practice, and acceptability of using Exception from Informed Consent (EFIC).

Conditions

Shock, Septic

Keywords

Sepsis; Septic shock; Pediatric; Fluid resuscitation; Saline; Lactated Ringer's; Crystalloid; Mortality; Pragmatic trial; Feasibility

Outcome Measures

Primary Outcomes (1)

• Compliance With Study Fluid Administration in the Assigned Study Arm

  Proportion of total crystalloids administered as saline in each arm during the intervention phase

  up 48 hours after randomization

Secondary Outcomes (2)

• Enrollment of Eligible Patients

  up to 6 months

• Acceptability of Enrollment Using "Exception From Informed Consent"

  up to 6 months

Other Outcomes (6)

• Mortality

  up to 90 days following randomization

• Hospital-free Days

  up to 28 days following randomization

• New Inpatient Dialysis

  Up to 90 days following randomization

Study Arms (2)

Lactated Ringer's fluid (LR)

EXPERIMENTAL

Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.

Drug: Lactated Ringer

0.9% "normal" saline fluid (NS)

ACTIVE COMPARATOR

0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.

Drug: Normal saline

Interventions

Lactated Ringer DRUG

LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).

Also known as: LR

Lactated Ringer's fluid (LR)

Normal saline DRUG

Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.

Also known as: 0.9% Saline, NS

0.9% "normal" saline fluid (NS)

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males or females age \>6 months to \<18 years
• Clinician concern for septic shock, operationalized as:
• a "positive" ED sepsis alert confirmed at the physician-led "sepsis huddle" OR
• a physician diagnosis of suspected septic shock requiring parenteral antibiotics and fluid resuscitation as per the ED sepsis management pathway
• administration of at least 20 mL/kg IV/ intraosseous (IO) fluid resuscitation
• Receipt of ≤40 mL/kg IV/IO crystalloid fluid prior to randomization
• Additional fluid deemed likely to be necessary to treat poor perfusion, defined as either hypotension or abnormal (either "flash" or \>2 second) capillary refill (as determined by clinician's judgment)10
• Parental/guardian permission (informed consent) if time permits; otherwise, EFIC criteria met

You may not qualify if:

• Clinician judgement that patient's condition deems it unsafe to administer either NS or LR (since patients will be equally likely to receive NS or LR at time of study enrollment), including (but not limited to):
• Clinical suspicion for impending brain herniation based on data available at or before patient meets criteria for study enrollment
• Known hyperkalemia, defined as non-hemolyzed whole blood or plasma/serum potassium \> 6 mEq/L, based on data available at or before patient meets criteria for study enrollment
• Known hypercalcemia, defined as plasma/serum total calcium \>12 mg/dL or whole blood ionized calcium \> 1.35 mmol/L, based on data available at or before patient meets criteria for study enrollment
• Known acute fulminant hepatic failure, defined as plasma/serum alanine aminotransferase (ALT) \>10,000 U/L or total bilirubin \>12.0 mg/dL, based on data available at or before patient meets criteria for study enrollment
• Known history of severe hepatic impairment, defined as diagnosis of cirrhosis, "liver failure", or active listing for liver transplant
• Known history of severe renal impairment, defined as current dependency on peritoneal dialysis or hemodialysis
• Known metabolic disorder, inborn error of metabolism, or primary mineralcorticoid deficiency (e.g., mitochondrial disorder, urea cycle disorder, amino acidemia, fatty acid oxidation disorder, glycogen storage disorder, congenital adrenal hypoplasia, Addison's disease) as reported by subject, LAR or accompanying caregiver, or as listed in the medical record
• Known pregnancy determined by routine clinical history disclosed by patient and/or legally authorized representative (LAR) (or other accompanying acquaintance)
• Known prisoner as determined by routine social history disclosed by patient and/or LAR (or other accompanying acquaintance)
• Known allergy to either normal saline or lactated Ringer's as determined by routine allergy history disclosed by patient and/or LAR (or other accompanying acquaintance) or as indicated in the medical record
• Indication of prior declined consent to participate based on presence of "PRoMPT BOLUS Opt-Out" bracelet

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• University of Utah: collaborator
• University of Pennsylvania: collaborator
• University of California, Davis: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (4)

• Weiss SL, Keele L, Balamuth F, Vendetti N, Ross R, Fitzgerald JC, Gerber JS. Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study. J Pediatr. 2017 Mar;182:304-310.e10. doi: 10.1016/j.jpeds.2016.11.075. Epub 2017 Jan 4.

  PMID: 28063688 BACKGROUND

• Emrath ET, Fortenberry JD, Travers C, McCracken CE, Hebbar KB. Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis. Crit Care Med. 2017 Jul;45(7):1177-1183. doi: 10.1097/CCM.0000000000002365.

  PMID: 28437373 BACKGROUND

• Semler MW, Rice TW. Saline Is Not the First Choice for Crystalloid Resuscitation Fluids. Crit Care Med. 2016 Aug;44(8):1541-4. doi: 10.1097/CCM.0000000000001941. No abstract available.

  PMID: 27428117 BACKGROUND

• Young P. Saline Is the Solution for Crystalloid Resuscitation. Crit Care Med. 2016 Aug;44(8):1538-40. doi: 10.1097/CCM.0000000000001844. No abstract available.

  PMID: 27153047 BACKGROUND

Related Links

• PRoMPT BOLUS Website
• Children's Hospital of Philadelphia Pediatric Sepsis Program Website

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Ringer's Lactate; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Scott L. Weiss, study co-PI
• Organization: The Children's Hospital of Philadelphia

WeissS@email.chop.edu

215-590-5505

Study Officials

• Fran Balamuth, MD PhD MSCE

  Attending Physician, Emergency Department

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Study participants, care provider, investigator, and outcomes assessor will not be masked to intervention allocation.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, open-label, randomized pragmatic clinical trial

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 14, 2017
• Study Start: January 24, 2018
• Primary Completion: August 31, 2018
• Study Completion: January 15, 2019
• Last Updated: August 5, 2019
• Results First Posted: August 5, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)