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: 1. Is there a minimum effective dose to treat seriously ill patients with convalescent plasma with COVID-19? 2. 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?
Specific objectives
1. Show the efficacy and safety of fresh plasma in different doses in severe cases and in
very severe cases.
2. 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.
3. 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:
1. . Severe ill group, convalescent plasma dose on day 0, evaluation on day +3 and if you
continue with the clinic and laboratories, a second dose of plasma may be administered.
Always watching the safety always (early and late transfusion reactions). Clinical
evaluation (including oxygenation) as well as laboratory (days +6, +9, +12, +15, +18,
+21 to find the necessary dose for response. The patients will be evaluated and if they
meet the response points, the minimum effective plasma dose will be recommended for
phase 2.
2. . Very severe ill group, convalescent plasma dose day 0, with evaluation on day +3, will
add another dose of plasma if there is no improvement clinic or laboratory, reevaluate
day +6 and if required, apply another dose of plasma if there will be not clinical or
laboratory improvement. Always watching security. It is reassessed clinically (including
respiratory parameters) on days +9, +12, +15, +18 and +21, to find the minimal dose
necessary. This sequential treatment will help reduce the risk of water overload and
also assess the presence of transfusion lung injury syndrome or TRALI. A second phase,
the dose and safety of treatment will be evaluated.
In the second phase , both early and late or B will be evaluated as follows:
to. Sever ill cases: plasma will be applied according to the dose you will find in phase 1b.
Security and response will be evaluated in this phase.
b. Very sever ill cases: Plasma will be applied according to the dose you will find in phase
1b and the safety and response phase will be evaluated.
It will also be open (the study will not be blinded), it will not be randomized, and it will
be controlled only by the severity of the patient and their characteristics of the disease
(severe vs. very severe), as well as being controlled by the amount of infusion of plasma
(minimum effective dose).
SECURITY ANALYSIS
The security analysis will be between the researchers in the group and another externak
group. They will analyze the first 5 patients in each group (severe and very severe), the
main objective for security analysis is going to be mortality related directly to plasma
infusion. Subsequently, every 20 patients in each group for phase 2 will be analyzed for
safety and response.
Biological: convalescent plasma
In phase 1, different amounts of convalescent plasma will be evaluated depending on the severity of the case.
In phase 2, both clinical, laboratory, imaging and viral presence (effectiveness) and safety will be evaluated.
Other Name: no apply
Inclusion Criteria:
All patients with COVID-19 test positive and... Severe ill patient
1. Respiratory difficulty
2. Sat O2 <93% without O2 but improves with the use of supplemental oxygen
3. CT scan image: COVID-19 compatible pneumonia
4. 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:
1. Respiratory difficulty that does not improve with supplemental oxygen, requiring
intubation and connecting to ventilatory support of no more than 72hrs or 3 days.
2. CT image: COVID-19 compatible pneumonia
3. 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.
4. Survival over 5 days.
Other inclusion criteria:
a) Pregnant women are accepted
Exclusion Criteria:
1. patients with asymptomatic/mild disease for COVID-19
2. Children less than 16 years old
3. patients with atypical pneumonia without COVID-19 diagnostic for PCR-RT
Hospital Del Issste Regional En Guadalajara Jalisco
Guadalajara, Jalisco, Mexico
Secretaria de Salud Del Estado de Sonora, Hospital General Del Estado
Hermosillo, Sonora, Mexico
Hospital Central Norte Pemex
Mexico City, Mexico
Luis M Villela, MD
+526624756529
luisvillela@yahoo.com
Diego Espinoza, MD
+526623862375
dr.espinoza.peralta@gmail.com
Luis M Villela, MD, Principal Investigator
ISSSTESON