CMV Refractory and Resistant Infection in Solid Organ Transplant Recipients in Argentina
2026年8月22日 更新者：EMILIO FELIPE HUAIER ARRIAZU、Hospital Italiano de Buenos Aires
Evaluation of Cytomegalovirus Refractoriness and Resistance in Solid Organ Transplantation in Argentina: A Multicenter Study
This study will describe the frequency and characteristics of refractory and resistant cytomegalovirus (CMV) infection in adults who received a solid organ transplant in Argentina between 2017 and 2024.
Researchers will review medical records from transplant centers across the country to identify episodes of CMV infection that did not respond adequately to standard antiviral treatment (refractory) or that showed genetic mutations associated with drug resistance.
The study will describe the clinical features, treatments used, and outcomes (including graft function and survival) of patients with these episodes, in order to better understand how common this problem is and what factors are associated with it in the local population.
調査の概要
状態
まだ募集していません
詳細な説明
Cytomegalovirus (CMV) remains one of the most frequent infections after solid organ transplantation (SOT), with important direct and indirect effects on graft and patient survival. While preventive strategies (prophylaxis and preemptive therapy) have reduced CMV-related disease and mortality, refractory and resistant CMV infection continues to be a major challenge, particularly in high-risk transplants (donor-positive/recipient-negative serostatus, and those receiving thymoglobulin induction). No epidemiological data on refractory or resistant CMV currently exist in Argentina.
This multicenter retrospective cohort study will include adult (≥18 years) solid organ transplant recipients from participating centers in Argentina who developed CMV infection within 18 months post-transplant, between January 1, 2017 and December 31, 2024. Cases meeting pre-specified operational criteria for refractory or resistant CMV infection will be identified from medical records. Refractory infection is defined as viral load that does not decrease or increases after two weeks of appropriate antiviral treatment; resistant infection is defined as refractory infection with documentation of at least one genetic mutation (UL97 and/or UL54) associated with antiviral resistance, confirmed through genotyping performed at the national reference laboratory (Instituto Malbrán).
Data will include demographic and transplant-related variables, immunosuppression regimen, virological monitoring, antiviral treatment lines and dosing, resistance genotyping results when available, and clinical outcomes including graft function, rejection episodes, and mortality at 90 days and one year. Data will be collected, coded, and stored in a centralized, de-identified database (REDCap) for descriptive and comparative statistical analysis.
研究の種類
観察的
入学 (推定)
200
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Emilio Felipe Huaier Arriazu, MD
- 電話番号：8165 / 9542 +549 011 49590200
- メール：emilio.huaier@hospitalitaliano.org.ar
研究連絡先のバックアップ
- 名前：Laura Alicia Barcan, MD
- 電話番号：8206 +549 1149590200
- メール：laura.barcan@hospitalitaliano.org.ar
研究場所
-
-
Buenos Aires F.D.
-
Buenos Aires、Buenos Aires F.D.、アルゼンチン、1199
- Hospital Italiano de Buenos Aires
-
副調査官：
- Emilio Felipe Huaier Arriazu, MD
-
コンタクト：
- EMILIO Felipe HUAIER ARRIAZU, MD
- 電話番号：8165 / 9542 +54911-49590200
- メール：emilio.huaier@hospitalitaliano.org.ar
-
コンタクト：
- Laura Alicia Barcan, MD
- 電話番号：8206 +54911-49590200
- メール：laura.barcan@hospitalitaliano.org.ar
-
副調査官：
- Astrid Smud, MD
-
主任研究者：
- Laura Alicia Barcan, MD
-
副調査官：
- Natalia Pujato, MD
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
サンプリング方法
非確率サンプル
調査対象母集団
Adult patients (≥18 years) who received a solid organ transplant (kidney, liver, heart, lung, pancreas, or combined transplant) at one of the participating centers in Argentina, and who developed cytomegalovirus (CMV) infection within 18 months following transplantation, during the period from January 1, 2017 to December 31, 2024.
Cases are identified retrospectively from the transplant databases and medical records of each participating center.
説明
Inclusion Criteria:
- Adult patients (≥18 years) who received a solid organ transplant (kidney, liver, heart, lung, pancreas, or combined) at a participating center in Argentina between January 1, 2017 and December 31, 2024
- Documented CMV infection within 18 months post-transplant
- Followed for at least 18 months from transplant and at least 12 months from CMV infection onset
Exclusion Criteria:
- Patients with incomplete medical records precluding assessment of CMV infection status or key study variables
- Patients not meeting the minimum follow-up period from transplant or from infection onset
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
|---|
|
CMV-infected SOT recipients
Adult solid organ transplant recipients (kidney, liver, heart, lung, pancreas, or combined transplants) who developed CMV infection within 18 months post-transplant between 2017 and 2024, followed to identify episodes meeting criteria for refractory or resistant infection
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of refractory or resistant CMV infection
時間枠：Within 18 months post-transplant, assessed retrospectively for the period January 2017 to December 2024
|
Proportion of solid organ transplant recipients with CMV infection who meet operational criteria for refractory infection (viral load unchanged or increased after 2 weeks of appropriate antiviral treatment) or resistant infection (refractory infection plus documented genetic mutation, e.g.
UL97 and/or UL54, associated with antiviral resistance)
|
Within 18 months post-transplant, assessed retrospectively for the period January 2017 to December 2024
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of overall CMV infection
時間枠：Within 18 months post-transplant, 2017-2024
|
Proportion of SOT recipients with any CMV infection (primary infection, reactivation, asymptomatic infection, or disease), stratified by transplanted organ
|
Within 18 months post-transplant, 2017-2024
|
|
Distribution of clinical forms of CMV infection
時間枠：Within 18 months post-transplant, 2017-2024
|
Classification of CMV episodes as primary infection, reactivation, asymptomatic infection, or CMV disease
|
Within 18 months post-transplant, 2017-2024
|
|
Frequency of antiviral resistance mutations
時間枠：From T3 (declaration of refractoriness) to T4 (episode resolution), up to 12 months
|
Proportion of genotyped refractory CMV episodes with ≥1 resistance-associated mutation (UL97 and/or UL54)
|
From T3 (declaration of refractoriness) to T4 (episode resolution), up to 12 months
|
|
Antiviral treatment lines and combination therapy use
時間枠：From T2 (treatment initiation) to T4 (negativization) or last available PCR if not resolved, up to 12 months
|
Number of antiviral treatment lines used per episode (1, 2, ≥3) and proportion of episodes receiving combination antiviral therapy (≥2 active agents ≥72h)
|
From T2 (treatment initiation) to T4 (negativization) or last available PCR if not resolved, up to 12 months
|
|
All-cause mortality
時間枠：90 days and 1 year post-episode onset
|
Proportion of patients who died at 90 days and at 1 year after the CMV refractory/resistant episode
|
90 days and 1 year post-episode onset
|
|
Graft outcome
時間枠：rejection following the CMV refractory/resistant episode Through 1 year post-episode onset
|
Proportion of patients with graft loss or rejection following the CMV refractory/resistant episode
|
rejection following the CMV refractory/resistant episode Through 1 year post-episode onset
|
|
Association between mutation type and antiviral treatment received
時間枠：From T2 (antiviral treatment initiation) to T4 (episode resolution), up to 12 months
|
Distribution of antiviral treatment regimens received (ganciclovir, foscarnet, letermovir, maribavir, cidofovir, combination therapy) according to mutation type detected (UL97 vs. UL54 vs. none)
|
From T2 (antiviral treatment initiation) to T4 (episode resolution), up to 12 months
|
|
Virologic response
時間枠：From T2 (treatment initiation) to T4 (confirmed negativization), up to 12 months, with censoring at last available PCR for patients not achieving negativization
|
Time to virologic negativization (two consecutive negative PCR results ≥7 days apart)
|
From T2 (treatment initiation) to T4 (confirmed negativization), up to 12 months, with censoring at last available PCR for patients not achieving negativization
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Chemaly RF, Chou S, Einsele H, Griffiths P, Avery R, Razonable RR, Mullane KM, Kotton C, Lundgren J, Komatsu TE, Lischka P, Josephson F, Douglas CM, Umeh O, Miller V, Ljungman P; Resistant Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials. Clin Infect Dis. 2019 Apr 8;68(8):1420-1426. doi: 10.1093/cid/ciy696.
- Kotton CN, Kumar D, Manuel O, Chou S, Hayden RT, Danziger-Isakov L, Asberg A, Tedesco-Silva H, Humar A; Transplantation Society International CMV Consensus Group. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025 Jul 1;109(7):1066-1110. doi: 10.1097/TP.0000000000005374. Epub 2025 Apr 9. No abstract available.
- Navarro D, Fernandez-Ruiz M, Aguado JM, Sandonis V, Perez-Romero P. Going beyond serology for stratifying the risk of CMV infection in transplant recipients. Rev Med Virol. 2019 Jan;29(1):e2017. doi: 10.1002/rmv.2017. Epub 2018 Oct 25.
- Mehta Steinke SA, Alfares M, Valsamakis A, Shoham S, Arav-Boger R, Lees L, Ostrander D, Forman MS, Shedeck A, Ambinder RF, Jones RJ, Avery RK. Outcomes of transplant recipients treated with cidofovir for resistant or refractory cytomegalovirus infection. Transpl Infect Dis. 2021 Jun;23(3):e13521. doi: 10.1111/tid.13521. Epub 2020 Dec 2.
- Tamzali Y, Pourcher V, Azoyan L, Ouali N, Barrou B, Conti F, Coutance G, Gay F, Tourret J, Boutolleau D. Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection. Transpl Int. 2023 Jun 15;36:11295. doi: 10.3389/ti.2023.11295. eCollection 2023.
- Aguado JM, Navarro D, Montoto C, Yebenes M, de Castro-Oros I. Incidence of refractory CMV infection with or without antiviral resistance in Spain: A systematic literature review. Transplant Rev (Orlando). 2024 Jan;38(1):100804. doi: 10.1016/j.trre.2023.100804. Epub 2023 Nov 6.
- Fisher CE, Knudsen JL, Lease ED, Jerome KR, Rakita RM, Boeckh M, Limaye AP. Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients. Clin Infect Dis. 2017 Jul 1;65(1):57-63. doi: 10.1093/cid/cix259.
- Kampouri E, Manuel O. Preemptive therapy versus universal prophylaxis: Time for reconciliation? Transpl Infect Dis. 2023 Apr;25(2):e14014. doi: 10.1111/tid.14014. Epub 2023 Feb 3. No abstract available.
- Stern M, Hirsch H, Cusini A, van Delden C, Manuel O, Meylan P, Boggian K, Mueller NJ, Dickenmann M; Members of Swiss Transplant Cohort Study. Cytomegalovirus serology and replication remain associated with solid organ graft rejection and graft loss in the era of prophylactic treatment. Transplantation. 2014 Nov 15;98(9):1013-8. doi: 10.1097/TP.0000000000000160.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年9月1日
一次修了 (推定)
2027年1月30日
研究の完了 (推定)
2027年3月1日
試験登録日
最初に提出
2026年7月26日
QC基準を満たした最初の提出物
2026年8月22日
最初の投稿 (実際)
2026年8月26日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月26日
QC基準を満たした最後の更新が送信されました
2026年8月22日
最終確認日
2026年8月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 7752 (CTEP)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
IPD プランの説明
Individual participant data will not be shared.
Study data are de-identified and coded using a randomly generated numeric key, in accordance with Argentine Personal Data Protection Law 25.326/00 (Habeas Data) and institutional confidentiality requirements.
Access is restricted to the principal investigator, and the database will be deleted upon completion of the statistical analysis.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。