Effectiveness of a preventive strategy for cytomegalovirus infection guided differently from a universal prophylactic strategy in kidney transplant patients - CYTOPREV

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515925-27-00

EudraCT number

2022-002556-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

Demonstrate, in CMV+ transplant patients, the effectiveness of an immuno-guided preventive strategy compared to the universal prophylactic strategy, in terms of CMV infection in the 6 months following kidney transplantation.

Secondary objectives 7

1. To demonstrate, in CMV+ transplant patients, the efficacy of an immuno-guided preventive strategy different from the universal prophylactic strategy, in terms of recourse to curative treatment of CMV infection, within 6 months following transplantation.
2. To demonstrate, in CMV+ transplant patients, the efficacy of an immuno-guided preventive strategy compared to the universal prophylactic strategy, in terms of the occurrence of CMV disease within 6 months following transplantation.
3. To evaluate the efficacy of the immuno-guided strategy compared to the universal prophylactic strategy in terms of prevention of CMV infection at 1 year post-transplantation.
4. To compare the T lymphocyte response at W+15 post-transplant in low- and high-risk patients in the experienced group
5. To compare the T lymphocyte response at W+28 post-transplant in low- and high-risk patients in the experienced group.
6. To compare the incidence of CMV reactivations (infection, infection requiring curative treatment, or disease) according to the donor's serological status (D+/R+ versus D-/R+) in the experienced group and the comparator group at 6 months and 12 months post-transplant.
7. Cost-effectiveness analysis carried out according to international standards (Husereau, 2013) and according to the recommendations of the French National Health Authority. The economic evaluation will be carried out at S+28 from the transplant between the 2 strategies to identify the costs induced by CMV avoided

Conditions and MedDRA coding

CMV

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 18 years ≤ Age ≤ 75 years
2. Renal transplant patient for 1 to 12 days
3. CMV seropositivity on the day of transplantation: IgG threshold =6 AU/mL CMIA CMV IgG, Architect i4000 (Abbott)) (Serology performed on D0, before the transplant)
4. Non-depleting inducing immunosuppressive treatment (Basiliximab) (implementation before the transplant)
5. Affiliation to a social security scheme
6. Patient having read and understood the information letter and signed
7. For women: - Woman of childbearing potential using effective contraception (Cf. CTFG) (estrogen-progestin or intrauterine device or tubal ligation) for at least 1 month and a negative β-HCG blood pregnancy test at inclusion, throughout the duration of study treatment and for at least 30 days after stopping study treatment. - Postmenopausal woman: confirmatory diagnosis (non-medically induced amenorrhea for at least 12 months before the inclusion visit) - Surgically sterile woman (absence of ovary and/or uterus)
8. Pour les hommes : - Stérilité chirurgicale, ou - Contraception mécanique (préservatif) pendant toute la durée du traitement à l’étude et pendant au moins 90 jours après la fin du traitement à l’étude, ou - Avec une partenaire en âge de procréer prenant une contraception efficace (Cf. CTFG) (oestro-progestatifs ou dispositif intra-utérin ou ligature de trompes) depuis au moins 1 mois à l’inclusion, pendant toute la durée du traitement à l’étude et pendant au moins 90 jours après l’arrêt du traitement, ou - Avec une partenaire ménopausée : diagnostic de confirmation (aménorrhée non médicalement induite depuis au moins 12 mois avant la visite d’inclusion), ou - Avec une partenaire chirurgicalement stérile (absence d’ovaire et/ou d’utérus).

Exclusion criteria 9

1. Age < 18 or > 75
2. Active CMV infection (detectable CMV DNAemia - peripheral CMV DNAemia ≥ 305 IU/mL)
3. Patient with hypersensitivity to valganciclovir, ganciclovir, aciclovir or valaciclovir or to any of the excipients
4. Lympho-depleting inducing immunosuppressive treatment (antithymoglobulins)
5. Neutropenia (neutrophils < 500/mm3) or thrombocytopenia (platelets < 25,000/mm3) or anemia (hemoglobin < 8g/dl) identified on routine care samples taken on the day of inclusion
6. Pregnant or parturient or breast-feeding woman or absence of proven contraception
7. Person deprived of liberty by an administrative or judicial decision or person placed under legal safeguard / sub-tutorship or curatorship
8. History of illness or psychological or sensory abnormality likely to prevent the subject from fully understanding the conditions required for their participation in the protocol or preventing them from giving their informed consent
9. Person participating in another interventional trial (Medicinal product)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with CMV infection within 6 months of transplantation.

Secondary endpoints 7

1. Proportion of patients requiring the use of curative antiviral treatment within 6 months after transplantation
2. Proportion of patients with CMV disease within 6 months of transplantation
3. Proportion of patients with CMV infection (CMV DNAemia ≥ 305 IU/mL (= 2.3 log IU/mL), CMV infection (CMV DNAemia ≥ 4 log IU/mL requiring curative treatment or CMV disease within the first year following transplant
4. Number of CMV-specific T lymphocytes (IE-1 and pp65) at W+15
5. Number of CMV-specific T lymphocytes (IE-1 and pp65) at W+28
6. CMV serological status of the donor (D+/R+ versus D-/R+)
7. Incremental cost-effectiveness ratio will be calculated for the period from randomization to the visit at S+28 post-transplantation for the experimental group (Arm ) compared to the comparator group (Arm ) with the average costs and efficacies for each strategy. The incremental cost-effectiveness ratio will be presented as additional cost per CMV infection avoided.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications