Study Objectives: The Increased Flow Utilizing Subcutaneously Enabled Pediatric Rehydration Study II (INFUSE II) evaluates whether recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous (SC) fluids are safe and effective in volumes no less than delivered via the intravenous (i.v.) route in mildly to moderately dehydrated infants and children. Methods: In this ongoing phase-4, open-label, randomized, stratified study, patients are children aged 1 month to < 3 years in emergency or pediatric inpatient departments with mild to moderate dehydration. Stratified based on body weight and dehydration severity, patients are randomly assigned to rehydration therapy (20 mL/kg isotonic fluid over 1 h and additional fluid as needed until deemed clinically rehydrated up to 72 h) via rHuPH20-facilitated SC or i.v. One mL rHuPH20 (150 U) is administered SC followed by SC isotonic fluids. Total fluid volume administered at a single infusion site is the primary study endpoint. Secondary endpoints include percentage successfully hydrated, time to urine output, total volume infused, and safety and health care provider ease-of-use assessments. Results: Interim data analysis was conducted on 41 patients (20 SC; 21 i.v.); mean age 1.6 years. Baseline Gorelick score indicated mild dehydration in 45% vs. 71%, and moderate in 55% vs. 29% in SC vs. i.v. groups, respectively. The primary efficacy outcome—mean total volume (standard deviation [SD]) infused at a single site—was 329 (216.7) mL SC vs. 560 (799.4) mL i.v. (Table 1). Least squares mean (LSM) (SD) for total volume infused, adjusted for infusion duration, was 466 (176.1) mL SC vs. 429 (175.9) mL i.v. Mean volume/body weight (SD) was 28 (17.2) mL/kg SC vs. 52 (77.2) mL/kg i.v.; LSM (SD), adjusted for infusion duration, was 42 (11.9) mL/kg SC vs. 39 (11.9) mL/kg i.v. Table 2 summarizes secondary endpoint results. Conclusions: Interim results suggest rHuPH20-facilitated SC infusion is safe and effective; duration-adjusted mean fluid volume infused was comparable for both routes, and a higher percentage of patients were successfully rehydrated via SC vs. i.v.

OBJECTIVES: The Increased Flow Utilizing Subcutaneously-Enabled (INFUSE)-Pediatric Rehydration Study was designed to assess efficacy, safety, and clinical utility of recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous rehydration in children 2 months to 10 years of age.METHODS: Patients with mild/moderate dehydration requiring parenteral treatment in US emergency departments were eligible for this phase IV, multicenter, single-arm study. They received subcutaneous injection of 1 mL rHuPH20 (150 U), followed by subcutaneous infusion of 20 mL/kg isotonic fluid over the first hour. Subcutaneous rehydration was continued as needed for up to 72 hours. Rehydration was deemed successful if it was attributed by the investigator primarily to subcutaneous fluid infusion and the child was discharged without requiring an alternative method of rehydration.RESULTS: Efficacy was evaluated in 51 patients (mean age: 1.9 years; mean weight: 11.2 kg). Initial subcutaneous catheter placement was achieved with 1 attempt for 46/51 (90.2%) of patients. Rehydration was successful for 43/51 (84.3%) of patients. Five patients (9.8%) were hospitalized but deemed to be rehydrated primarily through subcutaneous therapy, for a total of 48/51 (94.1%) of patients. No treatment-related systemic adverse events were reported, but 1 serious adverse event occurred (cellulitis at infusion site). Investigators found the procedure easy to perform for 96% of patients (49/51 patients), and 90% of parents (43/48 parents) were satisfied or very satisfied.CONCLUSIONS: rHuPH20-facilitated subcutaneous hydration seems to be safe and effective for young children with mild/moderate dehydration. Subcutaneous access is achieved easily, and the procedure is well accepted by clinicians and parents.