Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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:
CMV Viremia 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Letermovir Pill

Experimental: Study Group - All patients in the Study Group will receive virostatic prophylaxis with letermovir 480 mg qd (We will be utilizing Letermovir oral formulation of 240 mg or 480 mg as available).

No Intervention: Control Group - Patients in Controls will receive standard-of-care virostatic prophylaxis with valgancyclovir 450 mg bid.


Treatment: Drugs: Letermovir Pill
Patients in the Study Group will receive virostatic prophylaxis with letermovir 480 mg qd (We will be utilizing Letermovir oral formulation of 240 mg or 480 mg as available). n all patients the virostatic prophylaxis will be initiated between days 4 and 7 after heart transplantation and the duration of virostatic prophylaxis will be determined by the Quantiferon-CMV assay.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The rate of early CMV infections/disease during virostatic prophylaxis.
Timepoint [1] 0 0
baseline - 12 months
Secondary outcome [1] 0 0
The rate of leukopenia during virostatic prophylaxis
Timepoint [1] 0 0
baseline - 12 months
Secondary outcome [2] 0 0
The rate of neutropenia during virostatic prophylaxis
Timepoint [2] 0 0
baseline - 12 months
Secondary outcome [3] 0 0
The rate of late CMV infections/disease between virostatic discontinuation and 6 months thereafter.
Timepoint [3] 0 0
baseline - 12 months
Secondary outcome [4] 0 0
The time-course of the restitution of cell-mediated immunity during virostatic prophylaxis
Timepoint [4] 0 0
baseline - 12 months
Secondary outcome [5] 0 0
The rate of CMV resistance to virostatic therapy
Timepoint [5] 0 0
baseline - 12 months

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)
Recruitment outside Australia
Country [1] 0 0
Slovenia
State/province [1] 0 0
Ljubljana

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/ct2/show/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
bojan.vrtovec@kclj.si
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05432778