A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department.
BACKGROUND
Alternative treatment of dehydration is needed when intravenous (IV) or oral rehydration therapy fails. Subcutaneous (SC) hydration facilitated by recombinant human hyaluronidase offers an alternative treatment for dehydration. This clinical trial is the first to compare recombinant human hyaluronidase-facilitated SC (rHFSC) rehydration with standard IV rehydration for use in dehydrated children.


OBJECTIVE
This Phase IV noninferiority trial evaluated whether rHFSC fluid administration can be given safely and effectively, with volumes similar to those delivered intravenously, to children who have mild to moderate dehydration.


METHODS
The study included mild to moderately dehydrated children (Gorelick dehydration score) aged 1 month to 10 years. They were randomized to receive 20 mL/kg of isotonic fluids using rHFSC or IV therapy over 1 hour and then as needed until clinically rehydrated. The primary outcome was total volume of fluid administered (emergency department [ED] plus inpatient hospitalization). Secondary outcomes included mean volume infused in the ED alone, postinfusion dehydration scores and weight changes, line placement success and time, safety, and provider and parent/guardian questionnaire.


RESULTS
148 patients (mean age, 2.3 [1.91] years]; white, 53.4%; black, 31.8%) were enrolled in the intention-to-treat population (73 rHFSC; 75 IV). The primary outcome, mean total volume infused, was 365.0 (324.6) mL in the rHFSC group over 3.1 hours versus 455.8 (597.4) mL in the IV group over 6.6 hours (P = 0.51). The secondary outcome of mean volume infused in the ED alone was 334.3 (226.40) mL in the rHFSC group versus 299.6 (252.33) mL in the IV group (P = 0.03). Dehydration scores and weight changes postinfusion were similar. Successful line placement occurred in all 73 rHFSC-treated patients and 59 of 75 (78.7%) IV-treated patients (P < 0.0001). All IV failures occurred in patients aged <3 years; rHFSC rescue was successful in all patients in whom it was attempted. Both treatments were well tolerated. Clinicians rated fluid administration as easy to perform in 94.5% (69 of 73) of the rHFSC group versus 65.3% (49 of 75) of the IV group (P < 0.001). Parents/caregivers were satisfied or very satisfied with fluid administration in 94.5% (69 of 73) of rHFSC-treated patients and 73.3% (55 of 75) of IV-treated patients.


CONCLUSIONS
In mild to moderately dehydrated children, rHFSC was inferior to IV hydration for the primary outcome measure. However, rHFSC was noninferior in the ED phase of hydration. Additional benefits of rHFSC included time and success of line placement, ease of use, and satisfaction. SC hydration facilitated with recombinant human hyaluronidase represents a reasonable addition to the treatment options for children who have mild to moderate dehydration, especially those with difficult IV access. ClinicalTrials.gov identifier: NCT00773175.
Children's Healthcare of Atlanta at Scottish Rite, Atlanta, Georgia 30342, USA. Pip_spandorfer@PEMALLC.com
Philip R
PR
Spandorfer
Sharon E
SE
Mace
Pamela J
PJ
Okada
Harold K
HK
Simon
Coburn H
CH
Allen
David M
DM
Spiro
Keith
K
Friend
George
G
Harb
Francois
F
Lebel
D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003681:Dehydration / Q000175:diagnosis / Q000628:therapy*; D004636:Emergency Service, Hospital; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods*; D051548:Histone Acetyltransferases / Q000008:administration & dosage* / Q000009:adverse effects; D006760:Hospitalization; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage* / Q000009:adverse effects; D055103:Hypodermoclysis / Q000009:adverse effects; D007223:Infant; D007262:Infusions, Intravenous; D007552:Isotonic Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D000951:Antigens, Neoplasm; D007552:Isotonic Solutions; D011994:Recombinant Proteins; D051548:Histone Acetyltransferases; C115866:OGA protein, human; D006821:Hyaluronoglucosaminidase