Effectiveness of Adding Standard Plasma or COVID-19 Convalescent Plasma to Standard Treatment, Versus Standard Treatment Alone, in Patients With Recent Onset of COVID-19 Respiratory Failure. A Randomized, Three-arms, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- 30-days survival
研究概览
简要总结
To date no specific treatment has been proven to be effective for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) infection. It is possible that convalescent plasma that contains antibodies to SARS-Cov-2 might be effective against the progression of infection. Promising results have been shown by preliminary data from China cases. The investigators planned to compare effectiveness of adding COVID-19 convalescent plasma to standard therapy protocol (STP) versus adding plasma donated in pre-COVID era versus STP alone in patient with COVID-19 within 5 days from the onset of respiratory distress. STP at enrolment is the best evidence based therapy approved for treatment of COVID patients by regional Health system emergency committee.
详细描述
500-700 ml of Plasma will be collected by apheresis from COVID recovered donors showing the presence of neutralizing antibodies to SARS-Cov-2 (anti-SARS-Cov-2). All plasma will be screened for transmissible diseases according to italian law (Hepatitis B Virus,Hepatitis C Virus, Human Immunodeficiency Virus 1-2, Syphilis) plus adjunctive screening for Hepatitis A Virus and Hepatitis E Virus-RNA and Parvovirus B19-DNA as requested from Italian National Blood Authority. Apheresis will be divided in two/three units (170-300 ml each), virus inactivated with Riboflavin and ultraviolet light illumination technology and immediately frozen and stored separately from other plasma bags.
Enrolled patients will be stratified according to severity of respiratory failure and randomized in three arms: 1) Standard Therapy Protocol (STP), 2) Standard Therapy Protocol + 170-350 ml standard Plasma (SP) on day 1-3-5 after randomization, 3) Standard Therapy Protocol + 170-350 ml COVID-19 Convalescent Plasma on day 1-3-5 after randomization.
The three therapeutic units of COVID-19 Convalescent plasma will be chosen in order to minimize variations among patients in the total amount of infused SARS-Cov-2 antibodies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Only the two experimental arms are masked. COVID-19 convalescent plasma (CP) and standard plasma (SP) will be masked and delivered to the wards in identical bags; a tag printed as "PLASMA TRIAL" will cover the actual name of the product
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
- •Confirmed SARS-Cov-2 diagnosis by RT-PCR on nasopharyngeal swab or on bronchoalveolar lavage
- •Respiratory failure onset or progression within 5 days
- •Signed Informed Consent
排除标准
- •Pregnancy
- •Previous severe reactions to plasma transfusion
- •Unavailability of blood group compatible COVID-19 convalescent plasma
研究组 & 干预措施
Standard therapy protocol (STP)
STP is defined as the best evidence based therapy approved for treatment of COVID-19 patients by Regional Health System emergency committee. STP could be updated during the trial.
干预措施: Standard Therapy Protocol (STP) (Drug)
STP + Standard Plasma (SP)
STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
干预措施: Standard Therapy Protocol (STP) (Drug)
STP + Standard Plasma (SP)
STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
干预措施: STP + Standard Plasma (SP) (Other)
STP + COVID-19 Convalescent Plasma (CP)
STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
干预措施: Standard Therapy Protocol (STP) (Drug)
STP + COVID-19 Convalescent Plasma (CP)
STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
干预措施: STP + COVID-19 Convalescent Plasma (CP) (Other)
结局指标
主要结局
30-days survival
时间窗: 30 days after randomization
Proportion of patients alive 30 days after randomization
次要结局
- Clearance of viral load(On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months)
- Ventilator free survival(30 days after randomization)
- Sequential Organ Failure Assessment (SOFA) score(On day 0, 2, 4, 6, 10, 14, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months)
- Incidence of complications(Within 12 months)
- 6-months survival(6 months after randomization)
- Days in intensive care units (ICU)(From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months)
- Positivity for Immunoglobulin G to SARS-Cov-2(On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months)
- Any variation from Standard Therapy Protocol(From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed daily up to 2 months)
研究者
Paola Maria Manzini
Principal Investigator
A.O.U. Città della Salute e della Scienza