Valganciclovir vs. Letermovir for CMV Prophylaxis in Heart Transplant

Официальное название

VALganciclovir vs. LETermovir for Primary Prevention of CMV in Moderate to High-Risk Heart Transplant Recipients (The VALET-CMV Study)

Обзор

The purpose of this study is to compare the safety and efficacy of letermovir with valganciclovir for prevention of Cytomegalovirus (CMV) viremia in moderate to high risk serostatus heart transplant recipients.

Подробное описание

This trial is a multi-center prospective, two-arm randomized study designed to assess the safety of letermovir use as the primary prophylaxis for CMV in patients recently transplanted with a heart. Although there are findings to support the safety and efficacy profiles of letermovir in certain patient populations (kidney transplant, lung transplant, and hematopoetic stem cell transplant), there is a clear lack of prospective data to support use of letermovir at the primary prevention of CMV for patients recently transplanted with a heart. Thus, despite numerous studies showing letermovir to be non-inferior to valganciclovir with a substantial reduction in leukopenia and neutropenia, valganciclovir continues to be the initial CMV prophylaxis in heart transplant recipients. This study aims to either confirm the findings about letermovir as seen in other patient populations, or to highlight potential concerns about using letermovir in heart transplant patients. Patients who get letermovir will also be given acyclovir for HSV (Herpes Simplex Virus) prophylaxis for 6 months. Those taking valganciclovir will not need this as HSV is covered by valganciclovir. Low risk patients will also be monitored during this period for a better understanding of CMV disease in this population.

Вмешательства

• Препарат Letermovir
  CMV prophylaxis
• Препарат Valganciclovir
  Standard therapy for CMV prophylaxis

Первичные конечные точки

• Occurrence of leukopenia [Срок оценки: During the duration of CMV prophylaxis (6 months for moderate risk and 12 months for high risk from start of therapy)]
• Occurrence of neutropenia [Срок оценки: During the duration of CMV prophylaxis (Up to 6 months for moderate risk and up to 12 months for high risk from start of therapy)]

Вторичные конечные точки (3)

• Number of patients with any detectable CMV viremia after initiation of CMV prophylaxis [Срок оценки: 6 months after initiation of CMV prophylaxis]
• Number of patients with any detectable CMV viremia while on CMV prophylaxis [Срок оценки: During the duration of CMV prophylaxis (Up to 6 months for moderate risk and up to 12 months for high risk patients)]
• Number of patients with any detectable CMV viremia after completing CMV prophylaxis [Срок оценки: Within 6 months after completing CMV prophylaxis]

Критерии участия

Критерии включения

Patients who are >18 years of age who have received a heart transplant and have not started their CMV prophylaxis regimen will be included.

Критерии исключения

History of or suspected CMV disease within 6 months prior is excluded.

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

Профилактика

Центры проведения

США · 2 центра

• NYP-Weill Cornell — New York
• Columbia University/NYP Milstein Hospital — New York

Публикации

• Limaye AP, Budde K, Humar A, Vincenti F, Kuypers DRJ, Carroll RP, Stauffer N, Murata Y, Strizki JM, Teal VL, Gilbert CL, Haber BA. Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA. 2023 Jul 3;330(1):33-42. doi: 10.1001/jama.2023.9106. PMID 37279999
• Chong PP, Teiber D, Prokesch BC, Arasaratnam RJ, Peltz M, Drazner MH, Garg S. Letermovir successfully used for secondary prophylaxis in a heart transplant recipient with ganciclovir-resistant cytomegalovirus syndrome (UL97 mutation). Transpl Infect Dis. 2018 Oct;20(5):e12965. doi: 10.1111/tid.12965. Epub 2018 Jul 20. PMID 29989279
• Saullo JL, Miller RA. Cytomegalovirus Therapy: Role of Letermovir in Prophylaxis and Treatment in Transplant Recipients. Annu Rev Med. 2023 Jan 27;74:89-105. doi: 10.1146/annurev-med-042921-124739. Epub 2022 Nov 4. PMID 36332639
• Potena L, Solidoro P, Patrucco F, Borgese L. Treatment and prevention of cytomegalovirus infection in heart and lung transplantation: an update. Expert Opin Pharmacother. 2016 Aug;17(12):1611-22. doi: 10.1080/14656566.2016.1199684. Epub 2016 Jun 30. PMID 27340928
• Saullo JL, Baker AW, Snyder LD, Reynolds JM, Zaffiri L, Eichenberger EM, Ferrari A, Steinbrink JM, Maziarz EK, Bacchus M, Berry H, Kakoullis SA, Wolfe CR. Cytomegalovirus prevention in thoracic organ transplantation: A single-center evaluation of letermovir prophylaxis. J Heart Lung Transplant. 2022 Apr;41(4):508-515. doi: 10.1016/j.healun.2021.12.005. Epub 2021 Dec 22. PMID 35031206
• Rahman A, Lee C, Rahman S, Baranowska J, Moeller CM, Valledor AF, Rubenstein G, Oren D, Alnatour AT, Labarre B, Taek K, Bae D, Raikhelkar J, Lotan D, Defilippis EM, Yunis AA, Fried J, Latif F, Yuzefpolskaya M, Colombo PC, Lin E, Majure DT, Clerkin KJ, Choe J, Sayer G, Uriel N. Efficacy of Letermovir for Cytomegalovirus Prophylaxis in Heart Transplant Recipients with Moderate to High-Risk CMV Seros PMID 40562091

Идентификаторы

NCT: NCT07079735 · AAAV8422

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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