Efficacy of Liberal Versus Restricted IV Fluid Approach in the Management of Sickle Cell Vaso-Occlusive Crisis

Summary

Sickle cell disease (SCD) is a prevalent inherited blood disorder characterized by vaso-occlusive crises (VOCs), which lead to severe pain and complications. Despite hydration being a cornerstone of VOC management, the optimal fluid strategy remains uncertain. This study evaluates restrictive versus liberal fluid management strategies in patients with acute VOC. This multi-center, open-label, non-inferiority RCT will enroll patients with SCD presenting with acute VOC. Participants will be randomized to either a restrictive or liberal intravenous fluid management protocol. Primary outcome is pain score reduction. Secondary outcomes include time to pain resolution, ED length of stay, hospital admission rate, cumulative opioid dose, adverse events (incidence of fluid overload, pulmonary congestion), acute chest syndrome, incidence of acute kidney injury, revisit rates within 72 hours of ED discharge, need for intensive care or high-dependency unit admission, need for additional interventions, and 28 days overall mortality. Data will be analyzed using intention-to-treat principles. We hypothesize that a restrictive fluid strategy will achieve non-inferior pain control compared to a liberal strategy, while minimizing fluid-related complications. This study will provide evidence to inform clinical guidelines for fluid management in SCD patients experiencing VOCs.

Timeline

Start

2025-10-05

Primary completion

2028-08

Completion

2028-10

Publications

• Background Puri L, Nottage KA, Hankins JS, Anghelescu DL. State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease. Paediatr Drugs. 2018 Feb;20(1):29-42. doi: 10.1007/s40272-017-0263-z.
• Background Rizio AA, Bhor M, Lin X, McCausland KL, White MK, Paulose J, Nandal S, Halloway RI, Bronte-Hall L. The relationship between frequency and severity of vaso-occlusive crises and health-related quality of life and work productivity in adults with sickle cell disease. Qual Life Res. 2020 Jun;29(6):1533-1547. doi: 10.1007/s11136-019-02412-5. Epub 2020 Jan 13.
• Background Okomo U, Meremikwu MM. Fluid replacement therapy for acute episodes of pain in people with sickle cell disease. Cochrane Database Syst Rev. 2015 Mar 12;(3):CD005406. doi: 10.1002/14651858.CD005406.pub4.
• Background Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, Kutlar A, Seisa M, Stinson J, Strouse JJ, Yusuf F, Zempsky W, Lang E. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020 Jun 23;4(12):2656-2701. doi: 10.1182/bloodadvances.2020001851.
• Background Rosa RM, Bierer BE, Thomas R, Stoff JS, Kruskall M, Robinson S, Bunn HF, Epstein FH. A study of induced hyponatremia in the prevention and treatment of sickle-cell crisis. N Engl J Med. 1980 Nov 13;303(20):1138-43. doi: 10.1056/NEJM198011133032002.
• Background GBD 2021 Sickle Cell Disease Collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematol. 2023 Aug;10(8):e585-e599. doi: 10.1016/S2352-3026(23)00118-7. Epub 2023 Jun 15.

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