Nyretransplantasjonsbehandling eller profylakse for CMV -forebygging hos D+R -mottakere (KPoP)
Nyretransplantasjon Preemptive Therapy or Profylaxis (KPOP) for CMV-forebygging i D+R- Mottakere
This is a prospective, randomized multicenter trial of preemptive therapy (PET) vs. antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in adult D+R- kidney transplant recipients (KTR). Patients meeting study eligibility criteria and who have provided informed consent will be randomized (1:1) within 7 days of transplant to receive, in an open label design, either AP with valganciclovir 900 mg orally once daily or letermovir 480 mg orally once daily [both dose adjusted per Food and Drug Administration (FDA) label] for 200 days post-transplant), or PET (central lab weekly plasma polymerase chain reaction (PCR) monitoring for CMV deoxyribonucleic acidemia (DNAemia)) for 100 days post-transplant, with oral valganciclovir 900mg orally twice daily (or renally dosed per FDA label) at onset of CMV DNAemia at any level and continued until plasma CMV DNAemia is negative or below the level of quantitation in two consecutive weekly plasma samples. Study participants will be followed for pre-specified outcomes (clinical, laboratory, immunologic, safety) until withdrawal, death, or study closure, up to a maximum of 5.5 years post-transplant. Approximately 360 participants (180 participants in each group) will be randomized into the study.
Estimated Time to Complete Enrollment: 4 years
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Antatt)
Fase
- Fase 3
Kontakter og plasseringer
Studiekontakt
- Navn: Megan Gish
- Telefonnummer: 415-476-1985
- E-post: megan.gish@ucsf.edu
Studiesteder
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California
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San Francisco, California, Forente stater, 94117
- Rekruttering
- University of California, San Francisco School of Medicine
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Ta kontakt med:
- Puneet Sood, MD, MPH
- Telefonnummer: 415-353-1551
- E-post: puneet.sood@ucsf.edu
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Florida
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Miami, Florida, Forente stater, 33136
- Rekruttering
- University of Miami Miller School of Medicine
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Ta kontakt med:
- Yoichiro Natori, MD
- Telefonnummer: 305-355-5418
- E-post: yxn138@med.miami.edu
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Rekruttering
- Emory University School of Medicine
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Ta kontakt med:
- Aneesh Mehta, MD
- Telefonnummer: (404) 727-8435
- E-post: aneesh.mehta@emory.edu
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Nebraska
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Omaha, Nebraska, Forente stater, 68198
- Har ikke rekruttert ennå
- University of Nebraska Medical Center
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Ta kontakt med:
- Sias Scherger, MD
- Telefonnummer: 402-559-4000
- E-post: sscherger@unmc.edu
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Hovedetterforsker:
- Sias Scherger, MD
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New Jersey
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Livingston, New Jersey, Forente stater, 07039
- Rekruttering
- Robert Wood Johnson Health Network Barnabas Health
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Ta kontakt med:
- Francis Weng, MD
- Telefonnummer: (973) 322-5065
- E-post: francis.weng@rwjbh.org
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North Carolina
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Durham, North Carolina, Forente stater, 27708
- Rekruttering
- Duke University
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Ta kontakt med:
- Scott Sanoff, MD
- Telefonnummer: 919-620-5300
- E-post: Scott.sanoff@duke.edu
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Hovedetterforsker:
- Scott Sanoff, MD
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Texas
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Dallas, Texas, Forente stater, 75390
- Har ikke rekruttert ennå
- University of Texas Southwestern
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Ta kontakt med:
- Ricardo La Hoz, MD
- Telefonnummer: 214-645-6427
- E-post: ricardo.lahoz@utsouthwestern.edu
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Hovedetterforsker:
- Ricardo La Hoz, MD
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Virginia
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Richmond, Virginia, Forente stater, 23219
- Rekruttering
- Medical College of Virginia Commonwealth
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Ta kontakt med:
- Guarav Gupta, MD
- Telefonnummer: 804-828-4104
- E-post: gaurav.gupta@vcuhealth.org
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
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Subject has provided written informed consent.
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Age ≥ 18 years of age at the time of informed consent.
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Negative for IgG antibody to CMV as assessed in a CLIA-certified laboratory between 28 days prior to transplant and up to 10 days post-transplant but prior to randomization.
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Received a kidney transplant from a CMV seropositive (IgG positive) donor in the past 10 days prior to enrollment
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Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (SOC results within 7 days prior to transplant may be used), and must also agree to use a medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence from the time of enrollment through until discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.
NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy).
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If male, must agree to practice a barrier method of contraception or abstinence from the time of enrollment through 3 months after discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.
Exclusion Criteria:
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In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
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Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
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Allergy to valganciclovir/ganciclovir or Letermovir
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Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months prior to the qualifying CMV IgG serology as described in inclusion criteria #3 (this includes COVID convalescent plasma)
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Currently enrolled or anticipated enrollment in another interventional study that, in the opinion of scientific leadership team, could affect evaluation of the primary safety and/or efficacy outcomes.
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Most recent platelet count post-transplant <25,000/uL
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Most recent ANC performed post-transplant <1000/uL
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Multi-organ transplant (except simultaneous kidney-pancreas) within the past 7 days
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Prior or planned receipt of a hematopoietic cell transplant
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Baseline immunodeficiency prior to transplant, including but not limited to:
- Known or suspected HIV infection
- Congenital or acquired immunodeficiency
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Unacceptable immunosuppression
- Receipt of desensitization therapy prior to kidney transplant, or
- Receipt of an ABO-incompatible kidney transplant except A2 to blood type B
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Pre-emptive Therapy
900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction. |
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks. |
|
Aktiv komparator: Prophylaxis
900 mg of Valganciclovir given orally once daily to subjects for 200 days post transplantation. All dosages adjusted for renal dysfunction. |
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 200 days post transplantation as prophylaxis. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Forekomst av sluttpunktkomiteen (EC) -bekreftet CMV-sykdom (enten syndrom eller sluttorgan) med 1-års etter transplantasjon.
Tidsramme: Innen 1-års etter transplantasjon
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Innen 1-års etter transplantasjon
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Andel deltakere med etterforskerbestemt CMV-sykdom
Tidsramme: innen 1-års etter transplantasjon
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innen 1-års etter transplantasjon
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Tid i dager til biopsi-påvist akutt avvisning (Bipar)
Tidsramme: Fra randomiseringsdato til datoen for Bipar fra en hvilken som helst årsak, vurdert opptil 5,5 år
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Fra randomiseringsdato til datoen for Bipar fra en hvilken som helst årsak, vurdert opptil 5,5 år
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Tid i dager til å pode tap
Tidsramme: Fra dato for randomisering til datoen for tap av transplantasjon fra en hvilken som helst årsak, vurderte opptil 5,5 år
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Fra dato for randomisering til datoen for tap av transplantasjon fra en hvilken som helst årsak, vurderte opptil 5,5 år
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Tid i dager til døden
Tidsramme: Fra randomiseringsdato til dødsdatoen fra enhver årsak, vurdert opptil 5,5 år
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Fra randomiseringsdato til dødsdatoen fra enhver årsak, vurdert opptil 5,5 år
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Gjennomsnittlig estimert glomerulær filtreringshastighet (EGFR) i ml/min/1,73m2 ved 1, 2, 3 og 4 år etter transplantasjon
Tidsramme: 1, 2, 3 og 4 år etter transplantasjon
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1, 2, 3 og 4 år etter transplantasjon
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Non-inferiority of PET (within a 10% margin) vs AP for EC-confirmed CMV disease by 1-year post-transplant, contingent on failure to meet the primary superiority endpoint.
Tidsramme: by 1-year post-transplant
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Although the study sample size is powered to detect the superiority of one preventive strategy compared to the other, it is possible that the two approaches may have similar efficacy with respect to prevention of CMV disease. Therefore, should there be insufficient evidence to conclude superiority of one of the approaches, a key Secondary Outcome is a non-inferiority assessment of preemptive therapy to prophylaxis, assuming a non-inferiority margin of 10%. This margin is based on what is known about the effectiveness of the two approaches as published in literature and the potential that the two strategies could be similarly efficacious in preventing CMV disease. The success rate for the prophylaxis group is estimated to be ~80% based on a systematic review and meta-analysis with hypothesized success rates for the preemptive group expected to be higher. |
by 1-year post-transplant
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Abhijit P. Limaye, MD, University of California, San Francisco
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.
- Limaye AP, Budde K, Humar A, Vincenti F, Kuypers DRJ, Carroll RP, Stauffer N, Murata Y, Strizki JM, Teal VL, Gilbert CL, Haber BA. Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA. 2023 Jul 3;330(1):33-42. doi: 10.1001/jama.2023.9106.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Urogenitale sykdommer
- Mannlige urogenitale sykdommer
- Urologiske sykdommer
- Kvinnelige urogenitale sykdommer
- Kvinnelige urogenitale sykdommer og graviditetskomplikasjoner
- Nyresykdommer
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ringen
- Guanin
- Hypoksantiner
- Purinoner
- Puriner
- Ganciclovir
- Acyclovir
- Valganciklovir
Andre studie-ID-numre
- STUDY00020695
- 1R01AI184205-01 (U.S. NIH-stipend/kontrakt)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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