Cytomegalovirus InfectionsNCT07787767
CMV Refractory and Resistant Infection in Solid Organ Transplant Recipients in Argentina
An observational study of Cytomegalovirus Infections and Solid Organ Transplantation Recipient, run by Hospital Italiano de Buenos Aires at 1 site in Argentina.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections, Solid Organ Transplantation Recipient, Solid Organ Transplantation
- How many people
- 200 participants
- Where
- 1 siteArgentina
- Study dates
- 1 Sep 2026to 1 Mar 2027
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Emilio Felipe Huaier Arriazu, MD contact
Argentina1 site
Hospital Italiano de Buenos Aires
Buenos Aires, Buenos Aires F.D., 1199
EMILIO Felipe HUAIER ARRIAZU, MD, +54911-49590200 ext. 8165 / 9542, emilio.huaier@hospitalitaliano.org.ar
Laura Alicia Barcan, MD, +54911-49590200 ext. 8206, laura.barcan@hospitalitaliano.org.ar
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Cytomegalovirus Infections, Solid Organ Transplantation Recipient, Solid Organ Transplantation
- Keywords
- CMV, refractory infection, antiviral resistance, solid organ transplant, Drug Resistance, Viral
- Medical subject headings
- Cytomegalovirus Infections, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of refractory or resistant CMV infection
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)
Measured: Within 18 months post-transplant, assessed retrospectively for the period January 2017 to December 2024
Secondary outcomes (8)
Incidence of overall CMV infection
Proportion of SOT recipients with any CMV infection (primary infection, reactivation, asymptomatic infection, or disease), stratified by transplanted organ
Measured: Within 18 months post-transplant, 2017-2024
Distribution of clinical forms of CMV infection
Classification of CMV episodes as primary infection, reactivation, asymptomatic infection, or CMV disease
Measured: Within 18 months post-transplant, 2017-2024
Frequency of antiviral resistance mutations
Proportion of genotyped refractory CMV episodes with ≥1 resistance-associated mutation (UL97 and/or UL54)
Measured: From T3 (declaration of refractoriness) to T4 (episode resolution), up to 12 months
Antiviral treatment lines and combination therapy use
Number of antiviral treatment lines used per episode (1, 2, ≥3) and proportion of episodes receiving combination antiviral therapy (≥2 active agents ≥72h)
Measured: From T2 (treatment initiation) to T4 (negativization) or last available PCR if not resolved, up to 12 months
All-cause mortality
Proportion of patients who died at 90 days and at 1 year after the CMV refractory/resistant episode
Measured: 90 days and 1 year post-episode onset
Graft outcome
Proportion of patients with graft loss or rejection following the CMV refractory/resistant episode
Measured: rejection following the CMV refractory/resistant episode Through 1 year post-episode onset
Association between mutation type and antiviral treatment received
Distribution of antiviral treatment regimens received (ganciclovir, foscarnet, letermovir, maribavir, cidofovir, combination therapy) according to mutation type detected (UL97 vs. UL54 vs. none)
Measured: From T2 (antiviral treatment initiation) to T4 (episode resolution), up to 12 months
Virologic response
Time to virologic negativization (two consecutive negative PCR results ≥7 days apart)
Measured: From T2 (treatment initiation) to T4 (confirmed negativization), up to 12 months, with censoring at last available PCR for patients not achieving negativization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion30 Jan 2027 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Italiano de Buenos Aires
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Pharmaceuticals North America, Inc.
- Responsible party
- Principal investigator, EMILIO FELIPE HUAIER ARRIAZU, Hospital Italiano de Buenos Aires
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07787767
- Sponsor's protocol ID
- 7752
- Status last verified
- Aug 2026
- First submitted
- 26 Jul 2026
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
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.
PubMed 30358016Chemaly 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.
PubMed 30137245Mehta 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.
PubMed 33220125Tamzali 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.
PubMed 37398559Aguado 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.
PubMed 37949797Fisher 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.
PubMed 28369203Kotton 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.
PubMed 40200403Kampouri 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.
PubMed 36734636Stern 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.
PubMed 24837540