NCT05432778: CYPHER-TXPilot

Cytomegalovirus Prophylaxis With Letermovir in Heart Transplant Recipients

Recruiting now Phase 2 Last updated 9 November 2023

What this trial tests

Phase 2 trial testing Letermovir Pill in CMV Viremia in 90 participants. Currently enrolling.

Timeline

1 May 2023

Primary endpoint
1 August 2025

1 August 2026

Quick facts

Lead sponsor	University Medical Centre Ljubljana
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	90
Start date	1 May 2023
Primary completion	1 August 2025
Estimated completion	1 August 2026
Sites	1 location across Slovenia

Drugs / interventions tested

• Letermovir Pill — full drug profile →

Conditions studied

• CMV Viremia — all drugs for CMV Viremia →

Sponsor

University Medical Centre Ljubljana

Who can join

Adults 18 to 70, any sex, with CMV Viremia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.