Therapeutic Plasma Exchange Followed by Convalescent Plasma Transfusion in Severe and Critically Ill COVID-19 Patients
Phase: NA
Conditions: COVID-19 Pneumonia, COVID-19 Respiratory Infection, Acute Respiratory Failure, Acute Respiratory Distress Syndrome
Sponsor: Novacescu Alexandru

Therapeutic plasma exchange followed by convalescent 
plasma transfusion in severe and critically ill COVID-19 
patients: A single centre non-randomized controlled trial 
 
trial registration number: NCT04973488 
 
 
 
 
Date: 3 August, 2020 
 
 
            
 
 

 
Study design, setting and population 
A total of 38 Caucasian patients will be included in the present single center non-
randomized controlled trial. All patients included in the study will be adults (>18 years) 
who present with acute respiratory failure and ARDS, and have positive reverse 
transcriptase-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 virus upon 
hospital admission. ARDS is defined as acute-onset hypoxemia (P/F ratio <300) with >50% 
bilateral pulmonary opacities on chest imaging within 24-48 h that are not fully explained 
by congestive heart failure and that require ICU treatment and monitoring. Exclusion 
criteria are represented by any of the following: Pregnancy, patients with suspected or 
confirmed pulmonary embolisms and patients with terminal disease, patients < 18 years of 
age. Patients enrolled in the study will be divided equally, non-randomized, into two 
groups as follows: A treatment group who will benefit of sequential TPE and CVP 
transfusion in addition to the standard treatment for COVID-19, and a control group who 
benefit of only standard treatment for COVID-19 (antiretrovirals, corticosteroids, 
anticoagulants and antibiotics if deemed necessary) according to hospital protocols. 
All patients will provide written informed consent immediately after admission into the 
ICU regarding all the procedures performed during hospitalization, including the treatment 
scheme applied in the present study and the use of the resulting data in scientific research 
publications, with the assurance that they will remain anonymous. In cases where 
obtaining informed consent from the patients will not be possible due to their critical 
medical condition, a legal representative will be informed and provide written consent. The 
trial was approved by the Ethics Committee of ‘Pius Brinzeu’ Emergency Clinical County 
Hospital Timisoara (approval no. 91/03.08.2020). 
Study protocol 
The blood type of the patients will be determined immediately upon being admitted to the 
ICU. In the treatment group, a dual lumen, 14 French, dialysis catheter will be used for 
vascular access, by placing it in the femoral vein under echographic guidance. A single TPE 
session will be performed on the Infomed HF 440 machine (Infomed SA), with a 
plasma/blood separation ratio of 20%, using 40 ml/kg fresh frozen plasma as the 
substitute. The circuit will be anticoagulated with unfractioned heparin during the 
procedure. Upon completion of the TPE session, each patient from the treatment group will 
be transfused with 500 ml of ABO compatible CVP. Patients will be carefully monitored 

during both the TPE session and the CVP transfusion, and also after the procedures, in 
order to treat emerging complications. 
Patients from the treatment and control groups will receive standard treatment for COVID-
19 according to hospital protocols, consisting of corticosteroids, antiretrovirals, 
anticoagulants and antibiotics if deemed necessary. Patients from both groups will be 
anticoagulated with subcutaneous nadroparine (Fraxiparine; Aspen Pharma Trading) in 
therapeutic dosage, once every 12 h, adjusted according to bodyweight (≤70 kg: 3,800 Anti-
Xa IU; >70 kg: 5,700 Anti-Xa IU). Patients from the treatment and control groups will 
receive corticosteroids in the form of 16 mg dexamethasone (Dexamethason; Krka) divided 
into 2 doses, daily. Antiretrovirals administered will be the ones in the hosptital COVID-19 
protocol lopinavir/ritonavir (Kaletra; Hetero Labs, Ltd.), 300 mg b.i.d. and remdesivir 
(Veklury; Gilead Sciences), 200 mg loading dose, then 100 mg o.d. for 5 days. Antimalarial 
drugs will also be used, in the form of hydroxychloroquine (Plaquenil; Sanofi-Aventis), 400 
mg b.i.d. loading dose, then 200 mg b.i.d. Upon clinical (fever, chills, sweats or 
aspect/quantity of bronchial secretions) and paraclinical (leucocytosis, CRP or cultures) 
findings of infection, empiric antibiotics will be started, until de-escalation following 
culture results will be possible. Patients will be intensively monitored, and daily clinical 
and laboratory data will be collected during the ICU stay. Outcomes monitored will be 
survival at 30 days, oxygenation (P/F ratio) (normal ratio >300) and inflammatory 
markers [CRP (normal range 0-5 mg/l), LDH (normal range 135-225 U/l) and ferritin 
(normal range 30-400 µg/l)] at the 7-day follow-up, as assessed using ASTRUP analyses 
and blood tests. 
Statistical analysis plan 
Statistical data will be analysed using GraphPad Prism 8 (GraphPad Software, Inc.) and IBM 
SPSS Statistics 20 (IBM Corp.). The category variables will be characterized by value and 
percentage. Continuous variables will be presented as mean (± standard deviation) and 
median (interquartile range). Data distribution testing will be performed using the 
Shapiro-Wilk test. The numerical variables will be compared with the t-test for 
independent samples or the Mann-Whitney U test, depending on the type of distribution of 
the variables. The χ2 test (or Fisher's exact test) will be used for the nominal variables. The 
Kaplan-Meyer method with the log-rank (Mantel-Cox) test will be applied to evaluate the 
primary endpoint. Cox regression will be utilized to determine hazard ratio of the 
treatment group. All statistical tests will be calculated with 2 tails and P<0.05 will be 
considered to indicate a statistically significant difference. 
 

Local Ethics Committee Decision regarding Scientific Research in 
Human Subjects