Individualised Dose Optimisation of Ganciclovir in Immunocompromised Children Trial (ID-MAGIC)

Обзор

This study is being conducted at seven major children's hospitals in Australia and New Zealand to test a new approach for treating a virus, called cytomegalovirus in children with weakened immune systems. The researchers want to find out if using a web app to customise the dose of a medication called ganciclovir is better at clearing the virus over a six-week period compared to the standard method of giving the medication.

Подробное описание

Immunocompromised children between 1 months to 18 years with cytomegalovirus viraemia who are admitted to one of the participating sites will be enrolled into the trial if eligible (see eligibility criteria) and randomly allocated into two groups. Children in the 'control- standard dosing group' will receive standard intravenous ganciclovir treatment for cytomegalovirus viraemia at a standard dosing of at 5mg/kg IV BD. Children in the "intervention: individualised dosing using a web app group" will receive a personalised intravenous ganciclovir dose calculated using an individualised IV ganciclovir dosing app. This approach considers the patient's weight, creatinine level, and target drug exposure, allowing for tailored dosing based on individual pharmacokinetic parameters. The virological clearance by 6 weeks of the children in each of the two groups will be compared.

Вмешательства

• Препарат Standard dosing of IV ganciclovir
  IV ganciclovir at standard dosing
• Препарат Personalised dosing of IV ganciclovir
  IV ganciclovir at a personalised dosing calculated using a ganciclovir dosing web app

Первичные конечные точки

• The proportion of participants who achieve CMV virological clearance by 6 weeks [Срок оценки: 42 days]

Вторичные конечные точки (7)

• The proportion of participants who achieve CMV virological clearance before 3-weeks [Срок оценки: 21 days]
• The proportion of participants who develop CMV disease by 6 weeks [Срок оценки: 42 days]
• Difference between treatment groups in All-cause mortality by 6 months [Срок оценки: 6 months]
• The proportion of participants who develop drug resistant CMV infection by 6 months [Срок оценки: 6 months]
• The proportion of participants with treatment-related adverse effects (AEs) [Срок оценки: 42 days]
• Change in Quality of Life measured over 6 months using the EQ-5D-Y Questionnaire. [Срок оценки: 7 days, 42 days, 180 days]
• Difference between treatment groups in cost-effectiveness over the 6-month period following randomisation [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Immunocompromised patients including transplant recipients (haematopoietic stem cell transplant (HSCT), solid organ transplant (SOT)), those receiving chemotherapy or other immunosuppression or those with a known/suspected inborn error of immunity (determined by an immunologist); and
• Detectable clinically significant CMV viraemia and treating clinician determines that antiviral therapy is indicated.
• Willing to partake in the trial
• Willing/able to attend all follow up visits and capable of completing all trial assessments.
• Legally acceptable parent/guardian capable of providing consent on the participant's behalf.
• Treating clinician agreeable to child being enrolled in the trial.

Критерии исключения

• Current or prior CMV infection with documented genotypic resistance to GCV (UL97 and/or UL54); or
• Severe renal impairment (defined as estimated glomerular filtration rate (eGFR) <25mL/min); or
• Congenital CMV infection; or
• Life expectancy of less than 7 days as determined by the treating physician; or
• History of allergy, or adverse reaction to GCV, aciclovir or any component of the formulation; or
• Treating clinician determines that combination antiviral therapy is indicated for CMV infection; or
• Has received >3 days of IV GCV or foscarnet or oral valganciclovir for the treatment of CMV infection prior to enrolment; or
• Prior enrolment in the trial; or
• Current recipient of another investigational product used for the treatment of CMV infection, as part of a clinical trial.

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

Австралия · 6 центров

• Sydney Children's Hospital — Sydney
• The Children's Hospital at Westmead — Sydney
• Queensland Children's Hospital — Brisbane
• The Royal Children's Hospital — Melbourne
• Monash Children's Hospital — Melbourne
• Perth Children's Hospital — Perth

Новая Зеландия · 1 центр

• Starship Children's Hospital — Auckland

Публикации

• Heston SM, Young RR, Tanaka JS, Jenkins K, Vinesett R, Saccoccio FM, Martin PL, Chao NJ, Kelly MS. Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients. Open Forum Infect Dis. 2021 Dec 16;9(2):ofab639. doi: 10.1093/ofid/ofab639. eCollection 2022 Feb. PMID 35111869
• Chan S, Godsell J, Horton M, Farchione A, Howson LJ, Margetts M, Jin C, Chatelier J, Yong M, Sasadeusz J, Douglass JA, Slade CA, Bryant VL. Case Report: Cytomegalovirus Disease Is an Under-Recognized Contributor to Morbidity and Mortality in Common Variable Immunodeficiency. Front Immunol. 2022 Feb 15;13:815193. doi: 10.3389/fimmu.2022.815193. eCollection 2022. PMID 35242131
• El Haddad L, Ghantoji SS, Park AK, Batista MV, Schelfhout J, Hachem J, Lobo Y, Jiang Y, Rondon G, Champlin R, Chemaly RF. Clinical and economic burden of pre-emptive therapy of cytomegalovirus infection in hospitalized allogeneic hematopoietic cell transplant recipients. J Med Virol. 2020 Jan;92(1):86-95. doi: 10.1002/jmv.25574. Epub 2019 Sep 3. PMID 31448830
• Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Cost-effectiveness of Preemptive Therapy Versus Prophylaxis in a Randomized Clinical Trial for the Prevention of Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors. Clin Infect Dis. 2021 Nov 2;73(9):e2739-e2745. doi: 10.1093/cid/ciaa1051. PMID 32712663
• Tan SK, Waggoner JJ, Pinsky BA. Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients. J Clin Virol. 2015 Aug;69:179-83. doi: 10.1016/j.jcv.2015.06.006. Epub 2015 Jun 10. PMID 26209403
• Rastogi S, Ricci A, Jin Z, Bhatia M, George D, Garvin JH, Hall M, Satwani P. Clinical and Economic Impact of Cytomegalovirus Infection among Children Undergoing Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019 Jun;25(6):1253-1259. doi: 10.1016/j.bbmt.2018.11.028. Epub 2018 Nov 29. PMID 30502538
• Camargo JF, Kimble E, Rosa R, Shimose LA, Bueno MX, Jeyakumar N, Morris MI, Abbo LM, Simkins J, Alencar MC, Benjamin C, Wieder E, Jimenez A, Beitinjaneh A, Goodman M, Byrnes JJ, Lekakis LJ, Pereira D, Komanduri KV. Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients. Biol Blood Marrow Tra PMID 29217388
• Acquier M, Taton B, Alain S, Garrigue I, Mary J, Pfirmann P, Visentin J, Hantz S, Merville P, Kaminski H, Couzi L. Cytomegalovirus DNAemia Requiring (Val)Ganciclovir Treatment for More Than 8 Weeks Is a Key Factor in the Development of Antiviral Drug Resistance. Open Forum Infect Dis. 2023 Jan 23;10(2):ofad018. doi: 10.1093/ofid/ofad018. eCollection 2023 Feb. PMID 36817745

Идентификаторы

NCT: NCT06574789 · 107507

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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