NIH grant: Rapid Rehydration in the Treatment of Severe Hypernatremia (RaRe Treat) (1R01DK149765-01)

retained text

NIH grant 1R01DK149765-01: Rapid Rehydration in the Treatment of Severe Hypernatremia (RaRe Treat)
Institute: {'code': 'DK', 'abbreviation': 'NIDDK', 'name': 'National Institute of Diabetes and Digestive and Kidney Diseases', 'admin_org_id': '12500020', 'admin_funding_url': ''}. PI: Daniel  Shepshelovich. Award: $329000.
Start: 2026-08-01T00:00:00.
Project Abstract
We propose a pilot RCT comparing rapid hydration strategy to standard-of-care therapy for patients with severe
hypernatremia, for planning a large, multicenter efficacy trial. Hypernatremia (high serum sodium) indicates a
deficit in total body water. Hypernatremia is common in hospitalized patients and is associated with high mortality
rates, directly associated with hypernatremia severity (30-70% for severe hypernatremia). The traditional
approach is to correct hypernatremia slowly, not exceeding 0.5 mEq/L/hour or 10 mEq/L/day, using hypotonic
intravenous fluids, to avoid hypothetical cerebral edema and related neurological complications. This treatment
strategy is not supported by empirical clinical data in adults, and there are no convincing reports of neurological
harm in rapidly corrected patients.
Several retrospective studies, the largest published by the PI, have shown rapidly corrected patients had
significantly lower mortality rates, without neurological complications. Whether current recommendations reflect
the optimal balance between patient safety and potential harm is unknown. There is an unmet need for a RCT
to evaluate the best hydration strategy for patients with this common and life-threatening electrolyte disorder.
We propose a single center, feasibility RCT of 80 patients with severe hypernatremia (serum sodium ≥155
mEq/L) comparing rapid hydration to standard-of-care therapy, leading to a large, multicenter RCT powered to
detect lower 30-day mortality in the rapid hydration arm. The personalized, weight-based intravenous rapid
hydration protocol was developed by three experienced nephrologists, targeting a correction rate of 18
mEq/L/day until hypernatremia is resolved (serum sodium lower than 145 mEq/L). Treatment fidelity will be
assessed twice daily, with real-time interventions for any deviations from protocol. Safety monitoring will include
twice daily assessments of patients’ level of consciousness and presence of delirium using the Glasgow coma
scale and the brief confusion assessment method (bCAM), respectively, neurological function status
assessments using the modified Rankin score, brain imaging to exclude brain edema and daily chart reviews for
pre-specified neurological, cardiopulmonary or other complications. Aim 1 focuses on the feasibility of patient
identification, consenting, randomization, effective implementation of rapid hydration in the intervention arm
(primary endpoint), adverse event monitoring and 30-day survival ascertainment in both study arms. Aim 2
focuses on collecting preliminary safety and efficacy data informing the design of the subsequent RCT, including
any neurological or cardiopulmonary adverse events, 30-day survival and length of hospitalization.
This will be the first pilot RCT to prospectively compare treatment strategies for adults with hypernatremia, a
prevalent but understudied condition. The results of this study and the subsequent RCT will be novel and will
influence clinical practice, potentially improving survival and shortening hospitalizations.

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