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:
. 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.
. 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.