Levocarnitine for Reducing ESA Requirements in Hemodialysis Patients With Renal Anemia

Официальное название

Effect of Levocarnitine Injections on Reducing Erythropoietin-Stimulating Agent Requirements in Hemodialysis Patients With Renal Anemia

Обзор

Renal anemia is common in people receiving long-term hemodialysis and is usually treated with erythropoiesis-stimulating agents (ESAs). Some patients respond poorly and require high ESA doses, which increases treatment burden, cost, and potential side effects. Carnitine deficiency is frequent in hemodialysis because carnitine is lost during dialysis and its synthesis is reduced. Levocarnitine may improve red blood cell function and reduce the dose of ESA needed to maintain hemoglobin. This single-center, randomized controlled trial will test whether adding intravenous levocarnitine to standard care reduces ESA requirements in adults on maintenance hemodialysis who have renal anemia. Ninety-four participants (age 20-60 years) on thrice-weekly hemodialysis for ≥6 months and with hemoglobin \<10 g/dL will be randomly assigned (1:1) to: Intervention: Levocarnitine 1,000 mg IV three times per week, administered after each dialysis session, plus usual anemia care including ESA per unit protocol. Control: Usual anemia care including ESA per unit protocol without levocarnitine. Participants will be followed for 6 months. Hemoglobin, hematocrit, ESA dose, and the erythropoietin responsiveness index (ERI = monthly ESA dose ÷ \[dry weight × average hemoglobin\]) will be recorded monthly. The primary outcome is the ESA dose (units/week) at month 6. Secondary outcomes include ERI and monthly changes in hemoglobin and hematocrit, along with routine safety monitoring. If levocarnitine lowers ESA needs, the findings may offer a cost-effective strategy to optimize anemia management in hemodialysis patients.

Подробное описание

Background and Rationale. Carnitine supports erythrocyte membrane stability and energy metabolism. In maintenance hemodialysis, endogenous carnitine synthesis is reduced and dialytic losses occur, potentially contributing to ESA hyporesponsiveness. Small trials suggest that levocarnitine may reduce ESA dose requirements while maintaining target hemoglobin. Robust, region-specific evidence is limited.

Study Overview. This is a single-center, two-arm, randomized (1:1), open-label, parallel-group trial conducted at the Department of Nephrology, Shaikh Zayed Hospital, Lahore. Adults on thrice-weekly maintenance hemodialysis are randomized to: (A) adjunct levocarnitine 1,000 mg IV after each dialysis session, or (B) standard care without levocarnitine. ESA therapy is provided to all participants according to institutional practice, with dose adjustments based on routine hemoglobin monitoring. Study follow-up is 6 months, with monthly assessments of laboratory indices and ESA use. Full eligibility criteria, outcome measures (including the definition of the erythropoietin responsiveness index), intervention details, and visit schedule are specified in the corresponding PRS modules.

Statistical Considerations. The trial is powered (80% at α=0.05) to detect a between-group difference in ESA use at 6 months based on prior data; the planned sample size is 94 participants (47 per group). Analyses will follow the intention-to-treat principle, with supportive per-protocol analyses. Continuous outcomes will be summarized as mean±SD or median \[IQR\], and compared using appropriate two-sample methods. Prespecified subgroup and sensitivity analyses may adjust for baseline factors such as age, sex, BMI, and comorbidity status.

Safety and Monitoring. Adverse events and intercurrent illnesses are captured at each visit and via clinical record review. Any clinically significant events will be reported per institutional procedures. Data will be recorded on standardized case-report forms and managed to protect participant confidentiality.

Significance. Demonstrating reduced ESA requirements with levocarnitine while maintaining target hemoglobin could improve patient care and lower treatment costs in resource-constrained dialysis programs.

Вмешательства

• Препарат Levocarnitine Injection
  1,000 mg levocarnitine IV (slow IV push or infusion per unit policy) post-hemodialysis, three times weekly for 6 months (\~72 doses). Administered in the dialysis unit in addition to usual ESA-based anemia care.
• Другое Usual ESA-Based Anemia Care
  Standard-of-care anemia management using recombinant human erythropoietin (ESA) per unit protocol. Typical initial dosing: 50-100 U/kg/week if Hb \<10 g/dL (in 2-3 doses/week); 50 U/kg/week if Hb 10-11 g/dL; 25-50 U/kg/week as maintenance if Hb 11-12 g/dL. ESA dose adjusted monthly using ERI and Hb/Hct targets (generally Hb 10-12 g/dL).

Первичные конечные точки

• Weekly ESA dose at Month 6 (units/week) [Срок оценки: Month 6 (plus or minus 2 weeks) after randomization]

Вторичные конечные точки (1)

• Change in weekly ESA dose from Baseline to Month 6 (units/week) [Срок оценки: Baseline and Month 6 (±2 weeks)]

Критерии участия

Критерии включения

• Both male and female patients
• Patients aged 20-60 years.
• Patients undergoing maintenance hemodialysis three times a week for at least six months
• Patients having renal anemia

Критерии исключения

• Patients currently using any carnitine preparation as a supplement (to avoid confounding effects from additional carnitine intake).
• Patients on immunosuppressive drugs, steroids, or antibiotics (to avoid the influence of these medications on anemia and carnitine metabolism).
• Patients who have previously received levocarnitine in either oral or injected form (to eliminate any prior influence of levocarnitine on study outcomes).
• Patients with a history of blood transfusion within the past 6 months (to exclude the immediate impact of transfusions on hemoglobin levels and anemia management).
• Patients with acute inflammation (to prevent interference with study parameters as inflammation can affect anemia status).
• Patients with communication difficulties due to dementia or other factors (to ensure accurate symptom reporting and study adherence).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Morgans HA, Chadha V, Warady BA. The role of carnitine in maintenance dialysis therapy. Pediatr Nephrol. 2021 Aug;36(8):2545-2551. doi: 10.1007/s00467-021-05101-z. Epub 2021 Jun 18. PMID 34143302
• Kadiroglu AK, Yilmaz ME, Sit D, Kara IH, Isikoglu B. The evaluation of postdialysis L-carnitine administration and its effect on weekly requiring doses of rHuEPO in hemodialysis patients. Ren Fail. 2005;27(4):367-72. PMID 16060121
• Maruyama T, Higuchi T, Yamazaki T, Okawa E, Ando H, Oikawa O, Inoshita A, Okada K, Abe M. Levocarnitine Injections Decrease the Need for Erythropoiesis-Stimulating Agents in Hemodialysis Patients with Renal Anemia. Cardiorenal Med. 2017 Jun;7(3):188-197. doi: 10.1159/000462983. Epub 2017 Apr 20. PMID 28736559

Идентификаторы

NCT: NCT07160452 · TERC/SC/INT/2025/455

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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