Letermovir plus standard antiviral to clear CMV in lung transplant recipients

Combination Letermovir and Standard of Care Antiviral for Enhanced Antiviral Response in Cytomegalovirus Infection in Lung Transplant Recipients: A Pilot Trial

This will test whether adding letermovir to usual antiviral treatment helps clear CMV in lung transplant recipients with active infection by week 3.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07235683 on ClinicalTrials.gov

What this trial studies

This is a phase 4, randomized, placebo-controlled trial comparing letermovir plus standard-of-care (ganciclovir/valganciclovir) versus placebo plus standard-of-care in lung transplant recipients with active CMV viremia. Eligible participants have confirmed CMV viremia ≥1,000 IU/mL and have started standard antiviral therapy within the past 72 hours. The primary endpoint is clearance of CMV viremia by week 3, with safety monitored given prior concerns about myelosuppression from standard antivirals. The trial is being conducted at the University Health Network (Toronto General Hospital).

Who should consider this trial

Good fit: Ideal candidates are lung transplant recipients with confirmed CMV viremia (≥1,000 IU/mL) who have begun standard antiviral therapy within the past 72 hours and do not have contraindicating organ dysfunction or drug interactions.

Not a fit: Patients with known antiviral resistance, severe renal failure requiring dialysis, severe hepatic impairment, combined-organ transplants, contraindicated concomitant medications (e.g., cyclosporin, pimozide, ergot alkaloids), or those expected to receive CMV immunoglobulin during the initial three-week treatment phase are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, adding letermovir could speed viral clearance and potentially reduce toxic exposure to standard antivirals in lung transplant patients.

How similar studies have performed: Letermovir has demonstrated clear benefit as CMV prophylaxis in hematopoietic stem cell and some solid-organ transplant settings, but data for letermovir as a treatment are limited though small studies have shown reasonable responses, especially at lower viral loads.

Eligibility criteria

Inclusion Criteria:

* Recipient of a lung transplant.
* Has confirmed CMV viremia with a viral load ≥ 1000 IU/mL and will receive or has just started SOC antiviral treatment in the past 72h as per the decision of the treating physician.

Exclusion Criteria:

* Renal failure with Creatinine clearance \<15 mL/min or requiring dialysis
* Severe hepatic impairment (Child-Pugh Class C)
* Participating in another interventional clinical trial
* Combined transplant (e.g heart-lung, lung-liver)
* Known allergy or contraindication to any of the antiviral medications
* Known antiviral resistance.
* Patient receiving cyclosporin, pimozide or ergot alkaloids (due to significant drug interaction with letermovir).
* Patient receiving or expected to receive CMV immunoglobulin or IVIG during the initial three week treatment phase

Where this trial is running

Toronto, Ontario

• University Health Network, Toronto General Hospital — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Study coordinator: Atul Humar, MD, FRCPC

Conditions: CMV, Lung Transplant Recipient, CMV Disease, Lung Transplant