DETERMINATION OF THE DOSE AND EFFECTIVENESS OF CONVALESCENT PLASMA IN SEVERELY AND VERY SEVERELY ILL PATIENTS BY COVID-19
试验速览
- 阶段
- 1 期
- 入组人数
- 90
- 试验地点
- 3
- 主要终点
- early and late complications associated to convalescent plasma
研究概览
简要总结
The present study will try to respond first in an initial phase, what is the minimum effective dose necessary of convalescent plasma for getting better in severly ill (not intubated) or very severely ill (intubated) patients.
Once the dose will be determined by each type of patient group (severely ill vs. very severely ill) has been determined, phase 2 of the study will begin, where the safety and efficacy of the use of plasma will be evaluated based on clinical, imaging and laboratory criteria.
So, our hypotheses are:
- Is there a minimum effective dose to treat seriously ill patients with convalescent plasma with COVID-19?
- the plasma dose with the minimum effective effect will improve the clinical, laboratory and clearance conditions of the presence of the virus in the severely ill patient?
详细描述
Specific objectives
- Show the efficacy and safety of fresh plasma in different doses in severe cases and in very severe cases.
- Assess whether fresh plasma can overcome negative prognostic factors in very severe ill patients with COVID-19 infection. These factors are age, high SOFA score, and high D-dimer.
- To evaluate the titration of antiCOVID-19 antibodies and if its quantification is related to the therapeutic response.
The responses to drug treatments that exist in our country such as hydroxychloroquine ± azithromycin, lopinavir / ritonavir and tocilizumab (anti-IL-6) are very heterogeneous, with high cost and diverse and serious adverse events in some cases. Absent randomized-controlled studies and case series or small cohort studies have not been shown to be more effective than supportive treatments in these patients. One more factor is that intubated patients cannot swallow and these medications are for oral posology; the only way to administer is through a nasogastric tube, so we cannot assure that its absorption is as expected and that the blood levels do not reach therapeutic levels.
Therefore, we propose a treatment that in the first instance is in our hands, which has already proven to be effective in infection with highly pathogenic viruses such as Ebola virus, Lassar fever and other coronavirus infections (SARS1 in 2003, MERS 2012). With regard to convalescent plasma, two studies have recently been published, a series of 5 and another of 10 cases, seriously ill and with no response to the mentioned therapies (hydroxychloroquine ± azithromycin and lopinavir / ritonavir, among others). The outcomes in this series of cases have been reported satisfactory in most with few minimal adverse events (rash).
Since the convalescent plasma dose is very ambiguous in the case-series reported, we will try to find this dose. Therefore, in this initial phase, we divided it into two severity groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients with COVID-19 test positive and... Severe ill patient
- •Respiratory difficulty
- •Sat O2 <93% without O2 but improves with the use of supplemental oxygen
- •CT scan image: COVID-19 compatible pneumonia
- •one or more of at least: SOFA = 0 D-dimer ≥500 Age ≥ 65 years Comorbidities such as high blood pressure, diabetes mellitus type I and II, chronic kidney failure, controlled or cured cancer, ≥ 1 degree of obesity
- •Very severe ill:
- •Respiratory difficulty that does not improve with supplemental oxygen, requiring intubation and connecting to ventilatory support of no more than 72hrs or 3 days.
- •CT image: COVID-19 compatible pneumonia
- •one or more of at least: SOFA ≥1 Dimer D ≥ 750 Age ≥ 65 years Comorbidities such as hypertension, diabetes mellitus type I and II, Chronic Kidney Failure, Controlled or cured cancer, ≥ 1 degree of obesity.
- •Survival over 5 days.
- •Other inclusion criteria:
- •a) Pregnant women are accepted
排除标准
- •patients with asymptomatic/mild disease for COVID-19
- •Children less than 16 years old
- •patients with atypical pneumonia without COVID-19 diagnostic for PCR-RT
研究组 & 干预措施
single arm
Determine the convalescent plasma dose to be administered to two groups: one severely ill (not intubated) and one very severely ill (intubated).
Second phase: safety and efficacy of the plasma dose found in the same two types of patients.
干预措施: convalescent plasma (Biological)
结局指标
主要结局
early and late complications associated to convalescent plasma
时间窗: day 0 to day +30
Patients will be evaluated for adverse events during the plasma infusion up to 30 days after that. Especially mild and severe allergic reactions (anaphylaxis), other issues like TRALI.
improvement in tomographic image
时间窗: day -1 to day +12
before convalescent plasma infusion, the CT image will be compared and subsequently the evolution of images in the CT will be evaluated every 72 hours on 3 times .
test positivity for COVID-19
时间窗: day +6 to day +12
the patients will be evaluated on three occasions the positivity of the test (PCR-RT). If two of them are negative, it will be defined as a virus-free patient.
Clinical improvement
时间窗: day -1 to day +22
no fever, respiratory improvement and blood oxygenation (Sat02, Sat02 / Fi02), general laboratory improvement.
次要结局
- days at ICU(day 0 to day +30)
研究者
Luis Villela
MD,MSc
Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado