Effect of intratracheal Injection of Processed Autologous Serum Derived from Patients with covid-19 in oxygenation parameters and pulmonary Complications

To determine the effect of intratracheal injection of processed autologous serum derived from patients with COVID-19 in oxygenation parameters and pulmonary complications

Randomised, superiority, parallel group, phase 2, single-center trial with blinded outcome assessment. Randomisation will be performed using block randomisation (n=4).

This study will be conducted in a 22-bed ICU in northwest of Iran. Intubated patients with COVID-19 under mechanical ventilation will be enrolled. The patients will receive all the standard treatments. Also, the blood sample of patients will undergo centrifugation with 5000/min for separating plasma and then will be incubated for 8 hours. Thereafter, the plasma will be injected intratracheally for patients. For patients in control group, normal saline serum in the same volume will be intratracheally administered. This procedure will be performed every 3 days and the maximum number of administration will be 3 times in both groups. Patients and their next of kin as well as the researcher who will assess the outcomes will be blind to the study.

Inclusion criteria: intubated COVID19 patients Exclusion criteria: transplantation history, malignancy, thoracic surgery, autoimmune disease and active bacterial infection

In intervention group, the blood sample of patients will undergo centrifugation with 5000/min and then plasma will be incubated for 8 hours and injected intratracheally for patients. For control group, normal saline in the same volume will be intratracheally administered. This procedure will be performed every 3 days and the maximum number of administration will be 3 times in both groups.

Primary outcome: change in oxygenation Secondary outcomes: change in CO2; change in respiratory compliance; change in airway resistance

Initially, the blocks (n=4) with different arrangements of A and B will be defined. Considering the different probable arrangement of A and B, blocks will be numbered from 1 to 6. To enroll initial 4 patients into the study, one of the arrangements will be selected using the random digit table and the patients will be assigned into the A and B groups accordingly. For the next 4 patients, the arrangement pattern will be selected again and the patients will be assigned to the groups and this cycle will be repeated to achieve our intended sample size. Unpredictability of assignment and balancing the number of patients across the two groups during or at the end of the study are main advantages of this method. Notably, the patients will be assigned into the study based on the ICU date of admission and no body will be able to assign the patients to the specific group of interest.

The aim of double blinding is the avoidance of patients and researchers from being informed about the study intervention, so enrollment of patients in intervention and placebo groups will not be recognized. As the patients will be unconscious and under mechanical ventilation, they actually will not be aware of the group in which they are (intervention /placebo). The informed consent will be obtained from the patient's next of kin and they will thoroughly be informed about the study but they will be blind about the group in which their patient will be included. Also, the researcher who will assess the outcomes will not have any information about study enrollment and only primary investigator will know that. So, blinding will be performed for the researcher who will assess the study outcomes. As he/she will not be a member of treatment team and will be blinded to the study groups.

Will be available if needed