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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05432778




Registration number
NCT05432778
Ethics application status
Date submitted
20/06/2022
Date registered
27/06/2022
Date last updated
9/11/2023

Titles & IDs
Public title
Cytomegalovirus Prophylaxis With Letermovir in Heart Transplant Recipients
Scientific title
Cytomegalovirus Prophylaxis With Letermovir in Heart Transplant Recipients: A Non-randomized Cohort Pilot Study
Secondary ID [1] 0 0
01
Universal Trial Number (UTN)
Trial acronym
CYPHER-TXPilot
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
* heart transplant recipient (new)
* moderate (D+/R+ and D-/R+) or high (D+/R-) risk CMV serostatus
* signed informed consent for participation in the study
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* short-term mechanical circulatory support prior HTX
* ongoing CMV infection/disease
* D-/R- CMV serostatus
* heart re-transplantation
* need for intensified immunosuppression protocol

* >20% cytolytic alloantibodies prior transplant
* perioperative (within 7 days after HTX) allograft rejection > 1R
* immunoinduction with ATG
* pregnancy
* active participation in another interventional clinical trial
* know hypersensitivity to letermovir
* known hypersensitivity to valgancyclovir
* known hematological disorders (apart from anemia)

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Other
Name
University Medical Centre Ljubljana
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
CMV infection is the most prevalent infection after heart transplantation (HTX), occurring in up to 40-60% of the recipients. It most frequently occurs within the first 6 months after transplantation and commonly presents as an asymptomatic viral replication. Viral syndrome or tissue-invasive disease (gastroenteritis, pneumonitis, myocarditis or meningitis) are much less common. Even though CMV infection is generally treatable with virostatic therapy and/or CMV-specific immunoglobulins, direct effects of CMV infection (viral syndrome and tissue-invasive disease) and general and transplant-specific indirect effects of CMV infection have been associated with significant morbidity and mortality in HTX patient population, mainly due to graft loss, development of malignancies, or opportunistic infections. According to the latest consensus paper on CMV prophylaxis and treatment in solid organ transplant recipients, valgancyclovir (or its active form gancyclovir) represents a virostatic therapy of choice for CMV prophylaxis and treatment after HTX. However, valgancyclovir has an array of side effects including hematological (leukopenia, neutropenia, anemia, thrombocytopenia), neurologic (headache, insomnia), gastrointestinal (decreased appetite, diarrhea, vomiting and dyspepsia) and psychiatric (depression) disorders. These can either expose HTX patients to additional complications (e.g. leukopenia and/or neutropenia can result in systemic fungal infections), decrease patients' quality of life, or mandate a decrease in valgancyclovir dose, which exposes patients to an increased risk for CMV reactivation. Recently, letermovir (a novel CMV viral terminase inhibitor), was approved for CMV prophylaxis in allogeneic bone marrow transplant recipients as the placebo-controlled study showed that significantly less patients, treated with letermovir, developed CMV disease (37% vs. 60%; P\<0.001) and there was also a trend towards lower all-cause mortality. Data on bone marrow transplant recipients additionally suggest that letermovir is generally well tolerated with side effects limited to mild gastrointestinal symptoms (diarrhea, nausea). Importantly, myelosuppresive side effects of letermovir occur very rarely. Some encouraging data does exist on the use of letermovir in kidney transplant recipients, where a recently published proof-of-concept trial (N=27) suggested comparable safety and efficacy of leteremovir (N=18) and valgancyclovir (N=9): both treatment regimens resulted in similar time-course of viral load reduction and viral clearance and were well tolerated in terms of adverse events. Currently, a Phase III clinical trial is ongoing in renal transplant recipients (Clinicaltrials.gov: NCT03443869) to confirm this pilot data. However, to date, there is no published data on the use of letermovir in patients after HTX.

Based on the results in kidney transplantation, the aim of this pilot study is thus to evaluate the effects of letermovir-based CMV prophylaxis in heart transplant recipients.

The primary objective of the study is to investigate the efficacy of letermovir-based CMV prophylaxis in patients after heart transplantation.

The secondary objectives of the study are:

* to investigate the tolerability of letermovir-based CMV prophylaxis in patients after heart transplantation.
* to explore the potential correlation between letermovir-based CMV prophylaxis and restitution of cell-regulated immunity in patients after heart transplantation.
Trial website
https://clinicaltrials.gov/study/NCT05432778
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Bojan Vrtovec, MD, PhD
Address 0 0
Advanced Heart Failure and Transplantation Center, Universtiy Medical Center Ljubljana, Slovenia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bojan Vrtovec, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
+38615222844
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05432778