Oral vs Intravenous Fluid Therapy in Emergency Department Patients: Protocol for a Randomized Controlled Feasibility and Noninferiority Trial.

backgroundIntravenous fluid therapy is widely used in emergency departments (EDs) to treat hypovolemia and hypotension. However, its hemodynamic effects are often modest and short-lived. Intravenous fluid therapy requires a peripheral venous catheter, which increases the risk of complications such as catheter failure and phlebitis. Oral fluid therapy represents a simple, noninvasive alternative that has been shown in physiological studies to expand plasma volume and increase blood pressure. No randomized trial has compared oral with intravenous fluid therapy in a general adult ED population. Evidence regarding the feasibility of randomized comparisons of fluid administration modes and whether oral fluid administration can reliably deliver the prescribed volume remains limited.

objectiveThis study aims to evaluate the feasibility of conducting a randomized controlled trial of oral vs intravenous fluid therapy in ED patients requiring fluid replacement and to determine whether oral fluid therapy is noninferior to intravenous fluid therapy in achieving the prescribed fluid volume.

methodsThis investigator-initiated, multicenter, open-label randomized controlled feasibility and noninferiority trial will enroll 250 adult ED patients prescribed ≥1000 mL of intravenous crystalloid therapy. Participants will be randomized 1:1 to receive either oral fluids or intravenous crystalloid. The primary feasibility outcome is protocol adherence, defined as the proportion of randomized participants who receive the allocated route of administration without a major protocol deviation. The primary clinical outcome is the proportion of patients achieving the prescribed fluid volume during the ED stay, censored at 48 hours after randomization and analyzed using a noninferiority framework. Noninferiority of oral fluid therapy will be tested against the null hypothesis that the intravenous proportion exceeds the oral proportion by at least the noninferiority margin of 15 percentage points, using the difference in proportions with a 1-sided 97.5% CI (equivalent to a 2-sided 95% CI) from an exact proportion test. The sample size of 250 will provide 90% power at a 1-sided α of .025 under an assumed proportion of 85% in both arms.

resultsThe study was funded by the Region of Southern Denmark in May 2024. Recruitment began in October 2025 at 3 Danish EDs, and 85 participants have been recruited as of September 2026. Recruitment is projected to close in October 2026, with final 30-day follow-up projected for November 2026. No amendments to the protocol have been made. Results are expected to be published in summer 2027.

conclusionsThis trial will evaluate whether a randomized trial comparing intravenous and oral fluid therapy is feasible in ED patients and whether oral fluid therapy can achieve prescribed fluid volumes comparable to those achieved with intravenous therapy. The findings will inform the design of a future definitive effectiveness trial.

trial registrationClinicalTrials.gov NCT07361952; https://clinicaltrials.gov/study/NCT07361952. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/95459.