Exchange Transfusion Versus Plasma From Convalescent Patients With Methylene Blue in Patients With COVID-19 (COVID-19)

The aim of this project is to introduce way for treatment of patients with severe COVID-19 disease with respiratory complications.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Biological: exchange blood transfusion from normal donor; Biological: plasma from convalescent patients with COVID-19; Drug: Methylene Blue 5 MG/ML

Detailed Description

Study Tools AND/ OR procedure

The patients were subjected to the following:

Clinical parameters:

Complete history taking and thorough clinical examination

1. Laboratory parameters:
2. CBC with differential counts.
3. Reticulocytic count.
4. Blood film for shistocytes.
5. Serum ferritin and transferrin saturation.
6. D dimer.
7. Liver function tests, kidney function tests, electrolytes.
8. ESR.
9. CRP.
10. LDH.
11. Viral markers (HCV Ab, HBsV AG, HIV Ab).
12. ADAM'S 13 assays.
13. Serum soluble CD 25.

Other investigations:

1. Chest X ray.
2. Pelviabdominal US.
3. CT chest.
4. ECG.
5. Echocardiography

The patients will be divided into three groups, each group formed of 5 patients with severe COVID-19 or on mechanical ventilator receiving standard of care All the groups matched regarding age, sex and the severity of the disease.

Group I:

Will receive exchange transfusion by venesection of 500cc blood with good replacement of one unit packed washed RBCs daily for 3 days according to daily clinical and investigational follow up

Group II Will receive IV methylene blue 1 mg/kg IV over 30 minutes with 200 CC plasma from convalescent matching single patient by plasma extractor machine for 3 days according to daily clinical and investigational follow up.

Group III Will receive exchange transfusion by venesection of 500cc blood with good replacement of one unit packed washed RBCs and IV methylene blue 1 mg/kg IV over 30 minutes with 200 CC plasma from convalescent matching single patient by plasma extractor machine for 3 days according to daily clinical and investigational follow up.

N.B.: Convalescent plasma and regular blood will be taken from ministry of health after administrative approval All groups will receive

1. Low dose anticoagulant (LMWH 1 mg/kg/day).
2. Steroid (methyl prednisone 1 mg/ kg IV daily and according to patients' condition and presence of complications like hemophagocytosis).
3. All allergic precautions if needed like antihistaminics , epinephrine and steroid.

Close monitoring for:

1. Allergic reactions.
2. ECG changes daily.
3. Volume overload.
4. Complications of other comorbidities like DM or HTN.
5. Liver function and kidney function and organ dysfunction daily.

Terms of discontinuation:

Deterioration of clinical condition or organ functions.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mohamed M Moussa, MD; Phone Number: +201001553744; Email: drmohamed_metwali1@med.asu.edu.eg
• Study Contact Backup: Name: Essam A Hassan, MD; Phone Number: +201001839394; Email: essam.abdelwahed@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt, 11556
    • Recruiting
    • ain shams University
    • Contact: Mohamed M Moussa, MD; Phone Number: +201001839394; Email: drmohamed_metwali1@med.asu.edu.eg
    • Contact: Essam A Hassan, MD; Phone Number: +201001939394; Email: essam.abdelwahed@yahoo.com
    • Principal Investigator: Mohamed M Moussa, MD
    • Principal Investigator: Essam A Hassan, MD
    • Sub-Investigator: Ayman I Tharwat, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients are 18 years old or above.
2. Inpatients diagnosed as severe COVID - 19 disease according to WHO criteria.
3. CT chest with extensive lung disease (ground-glass and consolidative pulmonary opacities).
4. O2 saturation less than 93% resting.
5. Respiratory rate equal or more than 30 per minute.

Exclusion Criteria:

1. Patients with pregnancy and lactation.
2. Renal failure and heart failure.
3. Contraindication for plasma or blood transfusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exchange transfusion; Will receive exchange transfusion by venesection of 500cc blood with good replacement of one unit packed washed RBCs daily for 3 days according to daily clinical and investigational follow up	Biological: exchange blood transfusion from normal donor; IV method
Experimental: Methylene blue with plasma; Will receive IV methylene blue 1 mg/kg IV over 30 minutes with 200 CC plasma from convalescent matching single patient by plasma extractor machine for 3 days according to daily clinical and investigational follow up.	Biological: plasma from convalescent patients with COVID-19; IV method; Drug: Methylene Blue 5 MG/ML; IV method
Experimental: Exchange transfusion and methylene blue with plasma; Will receive exchange transfusion by venesection of 500cc blood with good replacement of one unit packed washed RBCs and IV methylene blue 1 mg/kg IV over 30 minutes with 200 CC plasma from convalescent matching single patient by plasma extractor machine for 3 days according to daily clinical and investigational follow up.	Biological: exchange blood transfusion from normal donor; IV method; Biological: plasma from convalescent patients with COVID-19; IV method; Drug: Methylene Blue 5 MG/ML; IV method

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement of condition	improvement of general condition of the patients as the ventilator parameters and serum level of ferritin , D dimer, CBC, oxygen level in blood and patient o2 saturation	three to five days days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in organs function with PFS and OS	change in the liver , kidney function and change in ferritin level with normal D Dimer	0ne month

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Mohamed M Moussa, MD, ain shams University; Study Director: Ayman I Tharwat, MD, ain shams University

Publications and helpful links

General Publications

• Chang D, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, Sharma L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. 2020 Mar 17;323(11):1092-1093. doi: 10.1001/jama.2020.1623.
• Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, Zimmer T, Thiel V, Janke C, Guggemos W, Seilmaier M, Drosten C, Vollmar P, Zwirglmaier K, Zange S, Wolfel R, Hoelscher M. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020 Mar 5;382(10):970-971. doi: 10.1056/NEJMc2001468. Epub 2020 Jan 30. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2020
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; Methylene blue; Exchange transfusion
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: FMASU P22/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No