Booster Dose of mRNA SARS-CoV-2 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response With or Without Immunosuppression Reduction - Protocol for a Randomised Controlled Trial (BECAME Study)
试验速览
- 阶段
- 4 期
- 发起方
- dafna yahav
- 入组人数
- 504
- 主要终点
- anti-spike protein titer above 50 AU/ml 2 weeks post vaccination
研究概览
简要总结
Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.
Methods and analysis: BECAME is a single center, open label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participant per arm will be also teste for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.
Ethics and dissemination: The trial is approved by local ethics committee of Rabin medical center (RMC-0192- 21). Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.
详细描述
All recipients more than 6 months post transplantation and at least 3 weeks following second vaccine dose will be approached and invited to a first study visit.
At first visit:
- Signed informed consent will be obtained from participants willing to participate by study investigators who usually work in the transplantation clinic.
- Anti-spike antibody response will be assessed using SARS-CoV-2 IgG II Quant (Abbott©) assay. Participants who have a documented seronegative test in the last 6 weeks will not be tested again.
Participants will be invited for an additional visit once negative serology will be reported, within 7 days of serology collection. At this second visit all participants who gave informed consent to participate in either the prospective non-randomised study or RCT will receive a single vaccine dose.
In addition, participants in the RCT will be randomised into two groups:
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
- •kidney transplant recipients that received two doses of BNT162b2 vaccine at least 3 weeks prior to enrollment, and were seronegative (IgG against the spike protein of SARS-CoV-2 below 50 AU/ml) at least two weeks after the second vaccine dose
- •Additional inclusion criteria for the RCT:
- •Recipients treated by three anti-rejection medications including: prednisone, tacrolimus, mycophenolate mofetil or mycophenolic acid.
- •Tacrolimus trough blood levels 5-10 nGr/ml (lower or higher doses will have to be adjusted before re-considering for inclusion)
排除标准
- •Past infection with SARS-CoV-2
- •Pregnancy
- •Age below 18 years
- •Active infection
- •Additional exclusion criteria for RCT only:
- •Recipients at a high risk for acute or chronic humoral rejection including:
- •Recipients with positive panel-reactive antibody (PRA) (any positive value) at any time before or after transplantation
- •Recipients that had an acute rejection in the last year
- •Recipients less than 6 months after transplantation
- •Recipients that are considered at high risk for rejection according to the primary care nephrologist
- •Recipients taking less than 3 anti-rejection medications
- •Recipients currently treated with mTOR inhibitors (everolimus, sirolimus) and/or azathioprine
- •Recipients treated with plasmapheresis in the previous 3 months
- •Recipients treated with eculizumab in the last year
- •Recipient treated with IVIG in the previous 3 months
- •Recipient treated with rituximab in the previous 6 months
结局指标
主要结局
anti-spike protein titer above 50 AU/ml 2 weeks post vaccination
时间窗: 2 weeks post vaccination
positive humoral response against SARS-CoV-2
次要结局
- anti-spike protein titer above 50 AU/ml 3-, 6-, and 12-months post vaccination(3-, 6-, and 12-months post vaccination)
- Log transformed titer of anti-spike protein weeks and 3, 6, and 12 months post vaccination(2 weeks and 3, 6, and 12 months post vaccination)
- Adverse events to booster dose using CTCAE v4.0 criteria(2 weeks post vaccine)
- Acute rejection of the allograft either documented by biopsy or clinically suspected, defined as increase in creatinine by 20% from baseline, without any other plausible explanation(2 weeks, 3,6, and 12 months post vaccination)
- positive PCR test to SARS-CoV-2 during the follow up period(until 12 months following vaccine)
- Positive PCR tests to VZV, CMV(during the follow up period)
- Number of hospitalizations (numerical count)(until 12 months following vaccine)
研究者
dafna yahav
Clinical Professor, Infectious Diseases Unit, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
Rabin Medical Center