Subcutaneous Rehydration Compared to Intravenous Rehydration (PEDs-II)

Subcutaneous Rehydration With Hylenex Compared to Intravenous Rehydration in Infants and Young Children With Mild to Moderate Dehydration

Randomized (1:1 ratio) study of subcutaneous (SC) versus intravenous (IV) fluid rehydration in mildly to moderately dehydrated pediatric patients.

Study Overview

• Status: Completed
• Conditions: Dehydration
• Intervention / Treatment: Drug: recombinant human hyaluronidase

Detailed Description

This is a prospective, randomized (1:1 ratio), open-label, parallel group, multicenter, multi-national, study of SC versus IV fluid rehydration in mildly to moderately dehydrated pediatric patients treated in the Emergency Department (ED), inpatient pediatric unit, and/or outpatient urgent care facility. It is expected that up to 186 patients, in order to achieve 148 evaluable patients, will be randomized in a 1:1 ratio to receive isotonic fluid rehydration by either SC administration with hylenex (150 Units) or IV without hylenex.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Florida
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital Children's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta - Scottish Rite
    • Dalton, Georgia, United States, 30721
      • North Georgia Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Michigan
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Children's Mercy Hospital & Clinics
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • UMDNJ/Robert Wood Johnson Medical School
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Children's Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Sciences Center
  • New York
    • Bronx, New York, United States, 10956
      • Children's Hospital at Montefiore
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital Emergency Department
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • Rainbow Children's and Babies Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center
    • Dallas, Texas, United States, 75235
      • Children's Medical Center Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children of either gender from one month to ≤10 years of age.
• Patients with mild or moderate dehydration
• Healthy child except for the underlying etiology for dehydration
• Pre-dehydration body weight ≥ 5th percentile for age
• Parents or legal guardian(s) available to provide informed consent.

Exclusion Criteria:

• Severe dehydration
• Shock or life-threatening situation (life expectancy < 10 days).
• Requirement for IV access for any indication other than for treatment of dehydration.
• Indwelling IV catheter, except for one intended only for collection of clinical laboratory specimens.
• Any condition precluding SC infusion or infusion site evaluation
• Any reason (prior to study enrollment) for a hospital admission or an extended stay in the ED for other than dehydration.
• Known hypersensitivity to hyaluronidase or hylenex.
• Known hyponatremia (< 130 milliequivalents per liter [mEq/L]) or hypernatremia (> 155 mEq/L).
• Known hypokalemia (< 3.0 mEq/L).
• Any medical condition likely to interfere with the patient's ability to fully complete all protocol-specified interventions, the ability to undergo all protocol-specified assessments, or likely to prolong the patient's need for medical attention beyond that required for treatment of dehydration.
• Participation in an investigational drug or device study within 30 days prior to enrollment in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subcutaneous; Isotonic fluid rehydration by SC administration with hylenex (150 Units in 1 mL)	Drug: recombinant human hyaluronidase; 150 Units in 1 mL; Other Names: Hylenex
Active Comparator: Intravenous; Isotonic fluid rehydration by IV	Drug: recombinant human hyaluronidase; 150 Units in 1 mL; Other Names: Hylenex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Volume of Fluid Administered at a Single Infusion Site, From the Start to the Cessation of Fluid Administration, for All Randomized Participants	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Total Volume of Fluid Administered at a Single Infusion Site, From the Start to the Cessation of Fluid Administration, for Non-rescued Participants	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Total Volume of Fluid Administered at a Single Infusion Site, From the Start to the Cessation of Fluid Administration, for All Rescued Participants	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Volume of Fluid Administered at All Infusion Sites, From the Start to the Cessation of Fluid Administration, for All Randomized Participants	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Total Volume of Fluid Administered at All Infusion Sites, From the Start to the Cessation of Fluid Administration, for All Randomized Participants Achieving > 200 mL	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest. The label for hylenex indicated precautionary wording recommending an upper limit on the volume of fluid (200 mL) administered subcutaneously to infants less than 3 years of age. In October 2008, the Food and Drug Administration (FDA) removed this wording from the label, thus negating the need for these data and associated analyses. The protocol was amended to reflect this label change; thus, this analysis was not conducted.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Total Volume of Fluid Administered at All Infusion Sites, From the Start to the Cessation of Fluid Administration, for Non-rescued Participants Achieving > 200 mL	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue. The label for hylenex indicated precautionary wording recommending an upper limit on the volume of fluid (200 mL) administered subcutaneously to infants less than 3 years of age. In October 2008, the FDA removed this wording from the label, thus negating the need for these data and associated analyses. The protocol was amended to reflect this label change; thus, this analysis was not conducted.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Total Volume of Fluid Administered at All Infusion Sites, From the Start to the Cessation of Fluid Administration, for All Rescued Participants Achieving > 200 mL	It was anticipated that most participants in this study would be hydrated through only one infusion site. For participants who received fluid at more than one administration site, a single infusion site was defined as the anatomical site at which the majority of the total infusion volume was infused. The term "anatomical site" was designated as: 1) the back; 2) left thigh; 3) right thigh; 4) abdomen; or 5) chest. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue. The label for hylenex indicated precautionary wording recommending an upper limit on the volume of fluid (200 mL) administered subcutaneously to infants less than 3 years of age. In October 2008, the FDA removed this wording from the label, thus negating the need for these data and associated analyses. The protocol was amended to reflect this label change; thus, this analysis was not conducted.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Flow Rate, Delivered Per Unit Time, for All Randomized Participants	The mean flow rate was averaged over any 60-minute period of time.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Flow Rate, Delivered Per Unit Time, for All Non-rescued Participants	The mean flow rate was averaged over any 60-minute period of time. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Flow Rate, Delivered Per Unit Time, for All Rescued Participants	The mean flow rate was averaged over any 60-minute period of time. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Flow Rate, Delivered by Volume Per Unit Body Weight Per Unit Time, for All Randomized Participants	The mean flow rate was averaged over any 60-minute period of time.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Flow Rate, Delivered by Volume Per Unit Body Weight Per Unit Time, for All Non-rescued Participants	The mean flow rate was averaged over any 60-minute period of time. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Flow Rate, Delivered by Volume Per Unit Body Weight Per Unit Time, for All Rescued Participants	The mean flow rate was averaged over any 60-minute period of time. Participants randomized to receive intravenous isotonic fluid were permitted to receive subcutaneous fluid administration by hylenex-facilitated infusion as rescue.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Achieving a Maximum Flow Rate of > 2 Milliliters Per Minute (mL/Min), as an Indication of Successful Hydration	The maximum flow rate was averaged over any 60-minute period of time.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Administered at Least 200 Milliliter (mL) Total Volume at a Single Infusion Site, From the Start to the Cessation of Fluid Administration	The number of participants administered at least 20 mL total volume was assessed.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants With the Indicated Type of Adverse Events	Adverse events (AEs) are defined as any untoward medical occurrence in a participant administered a product, which did not necessarily have a causal relationship with the treatment. Treatment-emergent adverse events (TEAEs) are defined as those events that occurred on or after the first injection device insertion attempt.	up to 7 days after hospital discharge
Number of Participants With Normal Physical Examination Findings at Baseline That Shifted to Abnormal at the End of Fluid Administration	Baseline was defined as the time prior to the single site fluid infusion. End of infusion was defined as the end of infusion of the single site fluid infusion for participants who had more than one fluid infusion. Not Rel Dehy = Abnormal, Not Related to Dehydration; Rel Dehy = Abnormal, Related to Dehydration. The investigator assessed findings as abnormal.	Baseline; after infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Change From Baseline in Heart Rate	Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the time prior to the single site fluid infusion. End of infusion was defined as the end of infusion of the single site fluid infusion for participants who had more than one fluid infusion.	Baseline; after infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Change From Baseline in Respiratory Rate	Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the time prior to the single site fluid infusion. End of infusion was defined as the end of infusion of the single site fluid infusion for participants who had more than one fluid infusion.	Baseline; after infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the time prior to the single site fluid infusion. End of infusion was defined as the end of infusion of the single site fluid infusion for participants who had more than one fluid infusion.	Baseline; after infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Mean Change From Baseline in the Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale Score	The infusion site was assessed for pain at two time points: after placement of the infusion device but before fluid infusion and at the end of infusion. Pain was recorded using the FLACC pain scale for children less than 3 years of age. Scores on the scale ranged from 0 (no hurt) to 10 (hurt worst).	Before infusion (Baseline); after infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants With the Indicated Type of Fluid Administered	Data are reported for the initial fluid administered.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Infusion Duration During the Initial Infusion	Infusion duration was assessed as a measure of the time required to complete the initial infusion of 20 mL/kg.	first hour of infusion
Change From Baseline in Hydration Status According to the Gorelick Assessment at the End of Fluid Infusion	Hydration status was assessed clinically using the Gorelick 10-item scale: general condition, quality of radial pulse, quality of respiration, skin elasticity, eyes, tears, mucous membranes, urine output, heart rate, and capillary refill time at the fingertip. Scores ranged from 0 (less severe impairment) to 10 (more severe impairment). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline; during the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Percent Change From Baseline in Body Weight	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) * 100.	Baseline; during the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants With the Indicated Type of Rescue Route Therapy Administered	Participants for whom parenteral access by the randomized route of administration could not be achieved after a reasonable number of attempts and for whom the investigator had deemed the access by that route a failure were expected to receive fluid administration by other means, designated as "rescue route" for the purpose of this study. This rescue route may have included venous cut-down, central venous line, interosseous access, etc., and for those participants initially randomly assigned to IV fluid administration, SC fluid administration by hylenex-facilitated infusion.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Classified With the Indicated Healthcare Provider Responses to the Questions Comprising the Healthcare Provider Global Satisfaction Questionnaire	A global assessment of overall satisfaction with the rehydration therapy by healthcare provider was performed at the end of SC or IV fluid rehydration utilizing a simple questionnaire. There were separate questionnaires for the two types of rehydration (SC and IV). Question 1: Was the participant successfully hydrated using the randomized route of administration?; Question 2: Overall, was the procedure of fluid infusion easy to perform?; Question 3: Were there any unacceptable side effects from the therapy?; Question 4: Would you consider using this hydration therapy for this indication in the future?	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Classified With the Indicated Healthcare Provider Responses to the Question: How Does This Therapy Compare to Your Experience With IV (for SC Group) / SC (for IV Group) Therapy?	A global assessment of overall satisfaction with the rehydration therapy by healthcare provider was performed at the end of SC or IV fluid rehydration utilizing a simple questionnaire. There were separate questionnaires for the two types of rehydration (SC and IV).	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Classified With the Indicated Parent/Guardian Responses to the Questions Comprising the Parent / Guardian Global Satisfaction Questionnaire	A global assessment of overall satisfaction with the rehydration therapy by healthcare provider was performed at the end of SC or IV fluid rehydration utilizing a simple questionnaire. There were separate questionnaires for the two types of rehydration (SC and IV). Question 1: Do you believe the method of therapy was successful in your child's rehydration?; Question 2: Have you or your child ever previously had IV fluids (for SC Group) / SC fluids (for IV Group)?; Question 3: If the response to Question 2 was "yes," how does this compare to prior experience with IV (for SC Group) / SC (for IV Group)?; Question 4: Should your child(ren) need rehydration treatment in the future, would you opt for this procedure?; Question 5: Should you need rehydration treatment in the future, would you opt for this procedure?; Question 6: What is your global satisfaction with the study procedure?	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants With the Indicated Number of Different Anatomical Administration Sites Needed After the Start of Fluid Administration	In the event that the degree of local infusion site swelling became unacceptable for any reason (e.g., a 30% or greater increase from the baseline circumference of the infused thigh or in the clinical judgment of the investigator), the infusion rate was decreased or the infusion site was changed.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Experiencing Reductions in Flow Rate	In the event that the degree of local infusion site swelling became unacceptable for any reason (e.g., a 30% or greater increase from the baseline circumference of the infused thigh or in the clinical judgment of the investigator), the infusion rate was decreased or the infusion site was changed.	During the infusion (single bolus dose of hylenex [1 hr], followed by subcutaneous fluid for 1 hour to 72 hours)
Number of Participants Who Received Needle Placement by People With the Indicated Level of Staff Training	Data were collected for the level of staff training for the person who performed the needle placement.	average of approximately 3 minutes
Number of Participants for Which the Indicated Number of Additional Personnel Was Involved in Needle Placement	Data were collected for the number of additional personnel involved in needle placement.	average of approximately 3 minutes
Time From the Start of Infusion to the Time of Emergency Department (ED) Discharge	Data are reported from the start of infusion to the time of ED discharge.	up to approximately 26 hours
Time From Randomization to the First Drop of Fluid Infusion	Data are reported for the time from randomization to the start of fluid infusion for all randomized participants.	up to approximately 110 and 220 minutes for the SC and IV arms, respectively
Number of Participants With the Indicated Number of Needle Stick Attempts Needed to Initiate Fluid Administration	Data are reported for the number of needle stick attempts needed to initiate fluid administration.	average of approximately 3 minutes
Number of Participants for Which the Indicated Type of Infusion Device Was Used	Data are reported for the type of infusion device used.	average of approximately 3 minutes
Number of Participants for Which the Indicated Gauge for Infusion Device Was Used	Data are reported for the gauge of infusion device used.	average of approximately 3 minutes
Number of Participants Discharged From the ED to Home or the Hospital	Participants were discharged from the ED to home or the hospital to continue hydration therapy.	up to approximately 26 hours
Number of Participants With the Indicated Reason for Rehospitalization Within 48 and 72 Hours After Discharge	Participants were discharged from the ED to home or the hospital to continue hydration therapy.	from randomization up to approximately 98 hours

Collaborators and Investigators

• Sponsor: Halozyme Therapeutics
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Coburn H Allen, MD, Baylor College of Medicine

Publications and helpful links

General Publications

• Spandorfer PR, Mace SE, Okada PJ, Simon HK, Allen CH, Spiro DM, Friend K, Harb G, Lebel F; Increased Flow Utilizing Subcutaneously-Enabled Pediatric Rehydration II (INFUSE-Peds II) Study Group. A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department. Clin Ther. 2012 Nov;34(11):2232-45. doi: 10.1016/j.clinthera.2012.09.011. Epub 2012 Oct 11.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 15, 2008
• First Submitted That Met QC Criteria: October 15, 2008
• First Posted (Estimate): October 16, 2008

Study Record Updates

• Last Update Posted (Actual): November 7, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: pediatric; hyaluronidase; rHuPH20; subcutaneous infusion; hylenex; recombinant human hyaluronidase
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Water-Electrolyte Imbalance; Dehydration
• Other Study ID Numbers: HZ2-08-03