CMV Refractory and Resistant Infection in Solid Organ Transplant Recipients in Argentina
2026년 8월 22일 업데이트: 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.
연구 개요
상태
상태
아직 모집하지 않음
정황
정황
상세 설명
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.
연구 유형
연구 유형
관찰
등록 (추정된)
등록
200
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
연구 연락처
- 이름: Emilio Felipe Huaier Arriazu, MD
- 전화번호: 8165 / 9542 +549 011 49590200
- 이메일: emilio.huaier@hospitalitaliano.org.ar
연구 연락처 백업
- 이름: Laura Alicia Barcan, MD
- 전화번호: 8206 +549 1149590200
- 이메일: laura.barcan@hospitalitaliano.org.ar
연구 장소
-
-
Buenos Aires F.D.
-
Buenos Aires, Buenos Aires F.D., 아르헨티나, 1199
- Hospital Italiano de Buenos Aires
-
부수사관:
- Emilio Felipe Huaier Arriazu, MD
-
연락하다:
- EMILIO Felipe HUAIER ARRIAZU, MD
- 전화번호: 8165 / 9542 +54911-49590200
- 이메일: emilio.huaier@hospitalitaliano.org.ar
-
연락하다:
- Laura Alicia Barcan, MD
- 전화번호: 8206 +54911-49590200
- 이메일: laura.barcan@hospitalitaliano.org.ar
-
부수사관:
- Astrid Smud, MD
-
수석 연구원:
- Laura Alicia Barcan, MD
-
부수사관:
- Natalia Pujato, MD
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
샘플링 방법
비확률 샘플
연구 인구
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.
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
그룹/코호트 수
1
코호트 및 개입
그룹/코호트그룹/코호트 |
|---|
|
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
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Incidence of refractory or resistant CMV infection
기간: 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
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Incidence of overall CMV infection
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
협력자
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- 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.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (추정된)
연구 시작
2026년 9월 1일
기본 완료 (추정된)
기본 완료
2027년 1월 30일
연구 완료 (추정된)
연구 완료
2027년 3월 1일
연구 등록 날짜
최초 제출
최초 제출
2026년 7월 26일
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
2026년 8월 22일
처음 게시됨 (실제)
처음 게시됨
2026년 8월 26일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
2026년 8월 26일
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
2026년 8월 22일
마지막으로 확인됨
마지막으로 확인됨
2026년 8월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- 7752 (CTEP)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
IPD 계획 설명
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.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .