Assessing the role of human recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR study.

BACKGROUND: Subcutaneous hydration has potential advantages over intravenous. Despite studies supporting the efficacy and safety of subcutaneous hydration it has not been studied extensively to date either with or without hyaluronidase.

OBJECTIVES: To compare flow rate, tolerability, and safety of gravity-driven subcutaneous fluid administration with and without recombinant human hyaluronidase (rHuPH20) in healthy volunteers.

DESIGN: Randomized, double-blind, placebo-controlled, within-subject trial.

SETTING: Contract research organization.

PARTICIPANTS: Fifty-four volunteers.

INTERVENTION: 24-gauge angiocatheters were placed subcutaneously in both upper arms. Each arm received rHuPH20 (150 U, 750 U, or 1500 U) or equal volume saline placebo. Immediately, 400 mL Lactated Ringer's (LR) solution was gravity-infused from a 100 cm height. In the pilot stage, 5 subjects also received a similar intravenous infusion.

MEASUREMENTS: Primary outcome was time to infuse 400 mL LR. Secondary outcomes included discomfort assessments, edema, arm circumference, time to recover to baseline arm circumference, subject and investigator global preference, and adverse events.

RESULTS: rHuPH20 150 U, 750 U, and 1500 U yielded mean flow rates of 383 +/- 119 mL/hr, 518 +/- 154 mL/hr, and 494 +/- 136 mL/hr, respectively, compared to their respective placebo rates of 82 +/- 30 mL/hr, 148 +/- 57 mL/hr, and 124 +/- 50 mL/hr. rHuPH20 was well tolerated.

CONCLUSIONS: In volunteers, clinically relevant fluid volumes can be rapidly delivered subcutaneously with rHuPH20 in a well-tolerated manner without a pump. These findings suggest that this method of hydration could potentially replace intravenous infusions in many clinical settings; further studies with rHuPH20, in patients, are warranted.