Novel Use of an Existing Vaccine (BCG) Alliance: The NUEVA Trial
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- Incidence of symptomatic rt-PCR-confirmed SARS-CoV-2 infection
研究概览
简要总结
The current COVID-19 epidemic threatens to overwhelm the capacity of many countries to meet their populations' health care needs. Although several vaccines specific for SARS-CoV-2 have been or are being developed, these require testing in animal and human safety studies and they are unlikely to be available during the expected peak periods of the growing epidemic. Two groups at especially high risk of infection and disease are front line health care workers working directly with COVID-19 patients and elderly residents of group homes or facilities that provide skilled nursing care to this frail population. Interim measures to protect these groups while we await a high efficacy vaccine are desperately needed.
Based on the capacity of BCG to (1) reduce the incidence of respiratory tract infections in children and adults; (2) exert antiviral effects in experimental models; and (3) reduce viremia in an experimental human model of viral infection, we hypothesize that BCG vaccination may induce (partial) protection against susceptibility to and/or severity of SARS-CoV-2 infection.
This study will evaluate the efficacy of BCG to reduce risk of infection by SARS-CoV-2 and mitigate COVID-19 disease severity in at risk health care providers.
A phase III randomized controlled trial provides the highest validity to answer this research question. Given the immediate threat of the SARS-CoV-2 epidemic the trial has been designed as a pragmatic study with a highly feasible primary endpoint, which can be continuously measured. This allows for the most rapid identification of a beneficial outcome that would allow other at-risk individuals, including the control population, to also benefit from the intervention if and as soon as it has demonstrated efficacy and safety.
详细描述
This study is a multi-center, prospective, double-blind, randomized placebo-controlled trial to assess the efficacy of intradermal TICE BCG (for intravesical use, Merck) BCG LIVE or placebo vaccine, in reducing the incidence of infection of SARS-CoV2 and severity of COVID-19 disease. This study proposes to examine BCG-induced nonspecific trained immunity to provide protection from SARS-CoV2 among health care workers who are likely to care for patients with COVID-19 illness, 18-64 years of age.
Up to 670 individuals will be screened to enroll 550 participants with a planned 50 person enrollment at USU site, 300 persons at Darnall Medical Center (CRDMC) and 200 persons at Brooke Army Medical Center (BAMC), resulting in 275 receiving BCG vaccine and 275 receiving placebo. To account for attrition prior to vaccination we will enroll up to 70 at USU, up to 350 at CRDMC and up to 250 at BAMC.
There are three phases in which research procedures will be completed: (1) initial screening for eligibility, consent, baseline testing; (2) enrollment, randomization, if pertains- prior to vaccination research blood draw for peripheral blood mononuclear cells (PBMC), and immunization with study vaccine (BCG or placebo); and (3) follow-up screening and testing.
Participants will be followed to assess whether infection with SARS-CoV-2 occurs:
Participants will complete intermittent surveys via an electronic system every 2 weeks to assess the presence of any flu-like symptom. Any positive response on the survey will trigger a nasopharyngeal swab to be collected to test for COVID-19 via rt-PCR.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Physicians, physician assistants, nurse practitioners, nurses, medics, respiratory therapists and other HCWs who are likely to care for patients with COVID-19 illness
- •Eligible for care in DoD facilities (DEERS eligible)*
- •18-64 years old
- •Willingness to permit review of medical records
- •Women of childbearing potential must be willing to use an effective form of birth control for 30 days post vaccination
排除标准
- •Previously (medical history) or currently infected or ill with COVID-19
- •Previous TB disease
- •Fever (>38 C) within the past 24 hours
- •Currently pregnant or breastfeeding or planning on becoming pregnant within 30 days of enrollment
- •Current serious underlying medical conditions including: diabetes mellitus, chronic kidney disease, or any other immunocompromising condition:
- •Known infection by Human Immunodeficiency Virus (HIV)
- •History of solid organ or bone marrow transplantation
- •Currently under chemotherapy
- •Currently on any anti-cytokine therapy
- •History of immunodeficiency (including history of anti B cell therapy)
- •Currently taking immunosuppressive drugs
- •Treatment with oral or intravenous steroids, defined as daily doses of 10mg prednisone or equivalent for longer than 3 months
- •Active solid or non-solid malignancy or lymphoma within the past two years
- •Suspicion of active viral or bacterial infection
- •Living with someone HIV+, who is immunocompromised, or is taking an immunosuppressive drug
- •Known allergy to (components of) the BCG vaccine or a serious reaction to prior BCG administration
- •Plan to terminate their employment at the participating health care facility or change duty stations within the next three months
- •Not in possession of a smartphone
- •Current participation in a COVID-19 interventional trial
研究组 & 干预措施
TICE BCG (for intravesical use, Merck) BCG LIVE
Participants randomized to the BCG arm will receive Tice® BCG (for intravesical use) BCG LIVE is a live freeze-dried vaccine made from an attenuated strain of Mycobacterium bovis. The freeze-dried vaccine will be delivered in vials, each containing 1 to 8 x108 colony forming units (CFU). Tice® BCG (for intravesical use) BCG LIVE will be reconstituted in ~5 mL of preservative-free saline, as needed for yielding 2- x107 CFU/ mL. [34] Administration of 0.1 mL will contain 2x106 CFU, which accounts for approximately 0.1 mg of the attenuated Mycobacterium bovis. Administration of 0.1 mL of diluted vaccine will be given per dose, intradermally. A sterile tuberculin 1mL syringe and sterile fine short needle (25 or 26 gauge with 3/8-3/4 length), will be used for each injection. The injection should be made slowly after inserting the needle ~2 mm into the superficial layer of the dermis of the upper arm (usually deltoid area), to make a symmetrical superficial bleb.
干预措施: Tice® BCG (for intravesical use) BCG LIVE strain of the BCG (Merck) vaccine (Drug)
placebo vaccine
Placebo will be administered in an intradermal route in the same location as the BCG vaccines: upper arm. Placebo will comprise 0.1 mL of the diluent (preservative-free saline) to ensure the same quantity and same color as the resuspended BCG vaccine, rendering the two indistinguishable.
干预措施: Preservative-free saline (Drug)
结局指标
主要结局
Incidence of symptomatic rt-PCR-confirmed SARS-CoV-2 infection
时间窗: 6 months
The primary outcome measure is the development of symptomatic COVID 19 infections. We will use the Cox proportional-hazards model to calculate hazard ratios for the development of COVID-19. This will be reported as the incidence of rt-PCR-confirmed symptomatic SARS-CoV-2 infection following BCG vaccination compared to that following placebo, starting from 3 days post-vaccination through 6 months.
次要结局
- incidence of Serology-confirmed infection with SARS-CoV-2(6 months)
- severity of COVID-19 disease(6 months)
- effect of prior adult immunization with other vaccines associated with trained immunity(6 months)
- symptomatic respiratory infection(6 months)