5: Rehydration Therapy: Hyaluronidase-Facilitated Subcutaneous Recombinant Human Hyaluronidase Versus Intravenous In Children

Article Outline

• Study Objectives
• Methods
• Results
• Conclusion
• Copyright

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Study Objectives 

Establishing intravenous (IV) access can be difficult in dehydrated children, who often have small, volume-depleted veins. Hyaluronidase-facilitated subcutaneous (HFSC) rehydration therapy with recombinant human hyaluronidase (rHuPH20) represents an alternative to IV in children with mild to moderate dehydration. A previously published multicenter, open-label, single-arm study (N=51) provided safety, efficacy, and tolerability data on HFSC rehydration therapy with rHuPH20 in children with mild to moderate dehydration. The objective of the INcreased Flow Utilizing Subcutaneously-Enabled Pediatric Rehydration II (INFUSE-Peds II) study was to evaluate whether in a pediatric population with mild to moderate dehydration, HFSC fluid administration with rHuPH20 can be given safely and effectively in clinically-appropriate volumes, no less than that delivered via IV administration.

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Methods 

Children aged 1 month to 10 years presenting to emergency departments with mild to moderate dehydration were enrolled in a Phase IV, multicenter, randomized, open-label, noninferiority, company-sponsored clinical trial. Patients were stratified by baseline dehydration severity and body weight and randomized to receive 20 mL/kg isotonic fluid via HFSC or IV over 1 hour and additional fluid, as needed, until clinically rehydrated for up to 72 hours. The primary outcome was total fluid volume administered at a single infusion site; secondary outcomes included dehydration symptoms, Gorelick dehydration score, ease of use measures, and safety evaluations.

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Results 

Enrollment (November 2008 to December 2009, 24 sites, N=148) is complete. Interim analysis is reported on 74 patients (37 HFSC, 37 IV), mean (SD) age 1.98 (1.56) years. Mean (SD) volume infused was 374 (292.1) mL HFSC versus 491 (645.3) mL IV. Mean (SD) duration of infusion at a single site was 2.8 (3.29) hours HFSC versus 6.0 (13.75) hours IV. When analysis of covariance was performed to adjust for duration of infusion, mean volume infused was 445 mL HFSC versus 419 mL IV. Mean improvement in dehydration score (95% CI) was −2.8 (−3.2, −2.4) HFSC and −2.4 (−3.0, −1.8) IV; mean weight change did not differ between groups. Initial catheter placement was successful in 97% HFSC versus 49% IV (OR=38.0; 4.7-306.9); median placement time (95% CI) was 0.6 minutes (0.25, 0.92) HFSC versus 5.0 minutes (1.0, 9.92) IV. Crossover for rescue treatment occurred in 0/37 HFSC versus 8/37 IV patients. Adverse events were mild to moderate in severity: pain (73% HFSC, 86% IV), erythema (73% HFSC, 6.9% IV), swelling (80% HFSC, 0% IV), and extravasation (0% HFSC, 3% IV).

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Conclusion 

In this interim analysis duration-adjusted mean fluid volume and resolution of dehydration signs and symptoms were comparable for the HFSC and IV routes, catheter placement took less time and was more often successful on the first attempt with HFSC versus IV, and HFSC infusions with rHuPH20 were generally well tolerated. These data suggest that the HFSC route represents a useful alternative to IV for isotonic fluid administration in this patient population. Final analysis of the complete data to be presented at the American College of Emergency Physicians' 2010 Research Forum will provide more definitive results from this trial.