ANZCTR - Registration

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

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/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]

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?

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

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

Bojan Vrtovec, MD, PhD

Address

Advanced Heart Failure and Transplantation Center, Universtiy Medical Center Ljubljana, Slovenia

Country

Phone

Fax

Contact person for public queries

Name

Bojan Vrtovec, MD, PhD

Address

Country

Phone

+38615222844

Fax

[email protected]

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05432778

Trial Review

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