Valganciclovir vs Letermovir for Infections in Heart Transplant

(VALET-CMV Trial)

Recruiting at 1 trial location

Overseen By Afsana Rahman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Columbia University

Disqualifiers: CMV disease history, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months for moderate risk, 12 months for high risk

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, letermovir and valganciclovir, to determine which is more effective and safer at preventing Cytomegalovirus (CMV) infections in heart transplant patients. CMV can cause serious problems, especially for those with weakened immune systems, such as heart transplant recipients. The trial includes different groups: one taking letermovir, another taking valganciclovir, and a low-risk CMV group that will not receive medication but will be monitored. Individuals who recently underwent a heart transplant and have not yet started CMV prevention are suitable candidates for this trial. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering a chance to advance heart transplant care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that letermovir is a safe option for preventing Cytomegalovirus (CMV) infections. Studies indicate it is well-tolerated, with no reports of serious side effects such as low white blood cell counts. Letermovir is already approved for use in other types of transplants, including kidney transplants.

Valganciclovir is also commonly used to prevent CMV in heart transplant patients. It is generally safe, though some individuals might experience side effects like low white blood cell or platelet counts. Despite these potential issues, it is widely considered effective and manageable with regular check-ups.

Both treatments have evidence supporting their safety, but they present different side effects. Participants should consider these differences when deciding to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Letermovir because, unlike standard treatments like Valganciclovir, it offers a different mechanism of action. Letermovir specifically targets the CMV terminase complex, which is crucial for viral DNA processing, potentially leading to fewer side effects related to bone marrow suppression—a common issue with Valganciclovir. This novel approach could mean a safer and more tolerable option for heart transplant patients at risk of CMV infections.

What evidence suggests that this trial's treatments could be effective for preventing CMV in heart transplant patients?

In this trial, participants will receive either letermovir or valganciclovir to prevent Cytomegalovirus (CMV) infections in heart transplant patients. Research has shown that letermovir is generally effective, with about 92.3% of patients successfully completing their treatment. It is well-tolerated and typically does not cause low white blood cell counts, a common side effect of many medications. Valganciclovir, another treatment option in this trial, is considered practical for clinical use. While it helps reduce CMV infections, some patients may still experience infections during treatment. Both treatments show promise, but their effectiveness can vary from person to person. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who recently received a heart transplant and are at moderate to high risk of developing CMV viremia, an infection caused by the cytomegalovirus. Participants should not have started any CMV prevention treatment yet and must not have had CMV disease within the last six months.

Inclusion Criteria

I am over 18, had a heart transplant, and haven't started CMV prevention treatment.

Exclusion Criteria

I have not had CMV disease in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either valganciclovir or letermovir for CMV prophylaxis, with valganciclovir covering HSV as well, while letermovir patients receive additional acyclovir for HSV prophylaxis

6 months for moderate risk, 12 months for high risk

Follow-up

Participants are monitored for CMV viremia and other outcomes after completing CMV prophylaxis

6 months

Long-term follow-up

Exploratory assessments of T cell response and TTV viral load to evaluate immunogenicity and risk of infection or rejection

6 months to 1 year after initiating CMV prophylaxis

What Are the Treatments Tested in This Trial?

Interventions

• Letermovir
• Valganciclovir

Trial Overview

The study aims to determine which drug is safer and more effective in preventing Cytomegalovirus (CMV) infections in heart transplant recipients: Valganciclovir or Letermovir.

How Is the Trial Designed?

Group I: Letermovir Experimental Treatment 1 Intervention

Patients with moderate to high risk CMV risk will get letermovir for prophylaxis for 6 months for moderate risk and 1 year for high risk

Group II: No treatment Active Control 1 Intervention

Low risk CMV patients who do not have an indication for CMV prophylaxis will be monitored

Group III: Valganciclovir Active Control 1 Intervention

Patients with moderate to high risk CMV risk will get valganciclovir for prophylaxis for 6 months for moderate risk and 1 year for high risk. This is standard of care

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1071916425002842

Efficacy of Letermovir for Cytomegalovirus Prophylaxis in ...

Most patients, 92.3%, were able to complete letermovir therapy for CMV prophylaxis post–heart transplantation. ABSTRACT. Background.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40562091/

Efficacy of Letermovir for Cytomegalovirus Prophylaxis in ...

Results: A total of 52 patients received letermovir for an average of 8.2 months (range, 1-35 months). The average time from transplantation to ...

3.

jhltonline.org

jhltonline.org/article/S1053-2498(25)02284-3/abstract

Letermovir prophylaxis and cytomegalovirus immune ...

Their results confirm that LET is associated with excellent tolerability, an absence of leukopenia and neutropenia, and no breakthrough CMV ...

4.

journalofinfection.com

journalofinfection.com/article/S0163-4453(24)00154-3/fulltext

Real-world experience with letermovir for cytomegalovirus ...

The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < ...

5.

jhltopen.org

jhltopen.org/article/S2950-1334(23)00047-2/fulltext

Cytomegalovirus infection in heart transplant recipients

This study analyzes the rates, risk factors, and outcomes of CMV among heart transplant recipients.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12335226/

De Novo Letermovir for Cytomegalovirus Primary ...

Currently, letermovir is approved for CMV prophylaxis in hematopoietic cell and kidney transplant recipients, but not for heart transplant recipients (HTR), ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05432778?cond=Letermovir&viewType=Table&rank=6

Cytomegalovirus Prophylaxis With Letermovir in Heart ...

CMV infection is the most prevalent infection after heart transplantation (HTX), occurring in up to 40-60% of the recipients. It most frequently occurs ...