Kidney Transplant Preemptive Therapy or Prophylaxis (KPoP) for CMV Prevention in D+R- Recipients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 360
- 试验地点
- 5
- 主要终点
- Incidence of endpoint committee (EC)-confirmed CMV disease (either syndrome or end-organ) by 1-year post-transplant.
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject or legally authorized representative has provided written informed consent.
- •Age ≥ 18 years of age at the time of informed consent.
- •Negative for antibody to CMV as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory between 28 days prior to transplant and 7 days post-transplant, but prior to enrollment, and no history of positive CMV serology Immunoglobulin G (IgG) antibody
- •Received a first kidney transplant from a CMV seropositive donor in the past 7 days prior to enrollment
- •Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (standard of care (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 1 month after discontinuation of either PET or AP.
- •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).
- •If male, and not surgically sterile, must agree to practice barrier method of contraception or abstinence from the time of enrollment through 1 month after discontinuation of either PET or AP.
排除标准
- •In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
- •Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
- •Allergy to valganciclovir/ganciclovir or Letermovir
- •Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma)
- •Currently enrolled in another interventional study that, in the investigator's opinion, could affect evaluation of the safety and/or efficacy outcomes
- •Most recent platelet count post-transplant <25,000/uL
- •Most recent ANC performed post-transplant <1000/uL
- •Multi-organ transplant or have undergone prior organ transplant
- •Baseline immunodeficiency prior to transplant:
- •Known or suspected human immunodeficiency virus (HIV) infection
- •Congenital or acquired immunodeficiency
- •Unacceptable immunosuppression
- •Receipt of desensitization therapy prior to kidney transplant, or
- •Receipt of a blood type A, B, or O-incompatible kidney transplant, or
- •Receipt or planned receipt of any of the following: belatacept, alemtuzumab, or rituximab
研究组 & 干预措施
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.
干预措施: Valganciclovir (Pre-emptive CMV Therapy) (Drug)
Prophylaxis
900 mg of Valganciclovir given orally once daily to subjects for 200 days post transplantation. All dosages adjusted for renal dysfunction.
干预措施: Valganciclovir CMV Prophylaxis (Drug)
结局指标
主要结局
Incidence of endpoint committee (EC)-confirmed CMV disease (either syndrome or end-organ) by 1-year post-transplant.
时间窗: Within 1-year post-transplant
次要结局
- Proportion of participants with investigator-determined CMV disease(by 1-year post transplant)
- 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.(by 1-year post-transplant)
- Time in days to biopsy-proven acute rejection (BIPAR)(From date of randomization until the date of BIPAR from any cause, assessed up to 5.5 years)
- Time in days to graft loss(From date of randomization until the date of graft loss from any cause, assessed up to 5.5 years)
- Time in days to death(From date of randomization until the date of death from any cause, assessed up to 5.5 years)
- Mean estimated glomerular filtration rate (eGFR) in mL/min/1.73m2 at 1, 2, 3, and 4-years post-transplant(1, 2, 3, and 4-years post-transplant)