Convalescent Plasma Therapy in Patients With COVID-19
Phase: PHASE1
Conditions: Convalescence, Corona Virus Infection, Plaque
Sponsor: Biofarma

Ethics Protocol for Health Research Involving Human Subjects  
 
 
 
Please fill the form below with brief summary and give check mark (X/V) inside the box or circle 
one answer choice which describe the research 
 
P: 
Protocol sequence number of CIOMS 2016 Protocol – Appendix 1  
S:  
Ethics Eligibility Standard (WHO-2011 and Ethic Research Committee & National Health   
Development Guideline 2017  
C:  
Checklist  
G:  
CIOMS 2016 Guideline  
IC:       CIOMS 2016 – Appendix 2  
 
Table of Contents : 
 
A. 
Research Title  
B. 
Summary of Research Proposal  
C. 
Ethical issues might be faced  
D. 
Summary of References  
E. 
Field Conditions 
F. 
Research Design  
G. 
Sampling  
H. 
Intervention 
I. 
Outcome Monitoring  
J. 
Termination of Research and Its Rationale 
K. 
Adverse Events & Complications  
L. 
Complications Handling  
M. 
Benefits  
N. 
Sustainability of Benefits Guarantee  
O. 
Informed Consent 
P. 
Guardian  
Q. 
Persuasion  
R. 
Confidentiality  
S. 
Analysis Plan  
T. 
Safety Monitoring  
U. 
Conflict of Interests  
V. 
Social Benefits  
W. 
Data Rights  
X. 
Publication   
Y. 
Funding  
Z. 
Ethics Commitment  
AA. 
References  
AB. 
Appendixes  
1. Curriculum Vitae of Main Researchers  
2. Case Report Form Sample  
 
 
 
 

 
2 
 
 
Ethics Protocol for Health Research Involving Human Subjects  
 
Please fill the form below with brief summary and give check mark (X/V) inside the box or circle 
one answer choice which describe the research 
 
P: 
Protocol sequence number of CIOMS 2016 Protocol – Appendix 1  
S:  
Ethics Eligibility Standard (WHO-2011 and Ethic Research Committee & National Health   
Development Guideline 2017  
C:  
Checklist  
G:  
CIOMS 2016 Guideline  
IC:       CIOMS 2016 – Appendix 2  
 
 
A. 
Research Title (p-protokol no 1)* 
Treatment towards COVID-19 Patients using Convalescent Plasma Therapy  
 
___________________________________________________________________________ 
1. Research Locations  :  
Gatot Soebroto Indonesia Army Central Hospital, Sulianti Saroso Infectious Disease Hospital, 
Persahabatan Hospital, Bio Farma, Eijkman Institute  
____________________________________________________________________________ 
Plan of Research Time (  Start –  Finish ) : April 2020 – April 2021 
 
   Yes  
    No 
2. Is this research multi-centre ?  
 
 
                
3. If multi-centre, does the research already have ethical approval from 
other centre / institution ?  
 
                
 
 
Identification (p10)  
 
1. Researcher  
( Please attach curriculum vitae of main researcher )  
Main researcher  
 
: Marliana Sri Rejeki, Clinical Pharmacologist, MD  
Institution 
 
 
: Gatot Soebroto Indonesia Army Central Hospital 
 
3. Research Member  
: ( attached )  
Institution 
 
 
: Gatot Soebroto Indonesia Army Central Hospital 
 
Sponsors (p9) 
Name   
 
 
: 
Address 
 
 
: 
V
V

 
3 
B. 
 Summary of Research Proposal  
1. Summary in 200 – 400 words ( written in language which can easily understood by 
common people, not physician / health worker )  
 
This virus began to be detected at the beginning of March 2020 and has already infected 1.677 
persons. By April 2020, 103 persons have already recovered meanwhile 157 persons died due to 
this virus. Globally, neither effective vaccine nor antiviral therapy has been approved as standard 
treatment for COVID-19 pandemic. Because of this situation, number of cases and deaths 
increase daily in Indonesia so development of therapy urgently needed to help faster recovery of 
COVID-19 patients. Convalescent plasma therapy from COVID-19 survivors is a promising 
strategy for COVID-19 patients’ recovery which hospitalized.1  
Interventional research was done with objectives as producing a good quality convalescent 
plasma from COVID-19 survivors, and to assess the safety of serial plasma transfusion to severe 
stage COVID-19 patients and its effect to clinical outcomes. The research questions which 
submitted are  Does plasma from COVID-19 survivors can neutralize virus at in-vitro experiment 
and produce good quality convalescent plasma ? and Whether convalescent plasma 
administration from COVID-19 survivors is safe to severe stage COVID-19? Could it produce 
better recovery, better prognosis and possibly heal COVID-19 ? Hypothesis (answer for research 
questions) is convalescent plasma therapy is safe and may improve clinical outcome in severe 
stage COVID-19 patients.  
 
Research and convalescent plasma therapy development divide into 2 activites which are in-vivo 
experiment ( intervention to observe safety  of plasma transfusion in COVID-19 patients ) then in 
parallel, in-vitro experiment ( convalescent plasma effect on neutralizing virus ). Safety of 
convalescent plasma will be observed in severe stage COVID-19 patients which hospitalized.  
 
Refinement process during in-vitro experiment involve Blood Transfusion Unit at Gatot Soebroto 
Indonesia Army Central Hospital; testing towards SARS-CoV-2 culture will be held at Eijkman 
Institute, meanwhile testing for level of convalescent plasma will be done by Bio Farma. 
Authorization for Blood Transfusion Unit of Gatot Soebroto Indonesia Army Central Hospital are 
extracting, testing, processing, storing and distributing convalescent plasma.  
 
Development of patients’ clinical condition before and after convalescent plasma therapy will be 
collected from automatic hospital medical record system. Hence, enhancement / alteration of 
clinical condition as outcomes are patients’ clinical condition, improvement of lung lesion from 
lung imaging, improvement of routine laboratorium parameter and lung function as recovery 
parameter of COVID-19 patients.2 
 
 
2. Research justification (p3). Please write down why this research need to be done, its 
benefit for population where this research will be located ( Country, Region, Local ) – 2/A 
Standard ( Justice )  
 
Results from this research are helping provision of anti-COVID-19 convalescent plasma products 
in Indonesia by finding right methods to process convalescent plasma from COVID-19 survivors 
and providing convalescent plasma material for further experiment which is efficacy testing 

 
4 
towards severe stage COVID-19 patients. Another benefit is providing knowledge for science to 
develop COVID-19 convalescent plasma in Indonesia.   
 
A. 
Ethical issues might be faced  
 
1. Researchers opinion regarding ethical issues that might be faced in this research and how to 
handle it (p4) – please adjust it with 7 standard value of ethical eligibility (S)  
 
Social values of this research are providing alternatives to handle urgent matters, giving 
contribution towards invention of treatment towards severe stage COVID-19 patients, and 
disseminating its result so that emergency counter measure of COVID-19 can be helped in various 
areas of Indonesia.  
 
Beside that, in this research, awareness of COVID-19 survivors are needed to give approval after 
explanation. Donors are not obligated to donate their blood. Donos independently decide whether 
they agree or disagree to donate their blood which will be converted to plasma. Likewise, 
hospitalized COVID-19 patients are obligated to give voluntarily approval after explanation. If 
patients’ condition do not enable to give consent, family or legal guardians are asked to give 
consent. So that, no coercion, no improper persuasion even no exploitation towards donors 
participation.   
 
Another important ethical issue is related to the less risks and greater benefits for COVID-19 
patients. Risks that related to passive convalescent plasma therapy both known risk and 
theoretical risk.  
 
First, known risk is risk related to blood plasma transfusion, including accidental infection by 
presence of other infectious disease agents and reaction towards serum such as rare 
immunologic reaction. However, with advancement technology on blood processing at blood 
transfusion unit, blood-transmission pathogens can be screened, blood type between donors & 
recipients can be matched, transfusion reaction can be supressed and also low risk of accidental 
other known infectious agents transmission. The only risk that reported was 1 COVID-19 patient 
suffered rash – local red spots and it disappeared in few days after plasma administration. Neither 
adverse events nor serious adverse events has been reported.  
 
Second, theoretical risk that involving infection escalation phenomenon, which depends on 
antibody (ADE – Antibody Dependent Enhancement). ADE might happens on several viral 
diseases and involve disease progression with certain antibodies. For Corona virus, several ADE 
mechanisms have been described and there is theoretical concern that antibordy towards 1 type 
of corona virus can escalate other viral infections. Because of convalescent plasma therapy 
proposal in COVID-19 pandemic will depend on level of good quality neutralizing antibody towards 
the same virus, COVID – 19, possibility of ADE will be small, or even not at all.  
 
Available evidences for usage of convalescent plasma on patients with SARS1 and MERS 
showed that plasma transfusion was safe and following infection screening according to blood 
bank standard.  
 
 

 
5 
Other theoretical risk is antibody administration towards COVID-19 patients assumed can prevent 
disease by weakening immune system which makes the recipients more vulnerable to re-
infection. In this matter, passive antibody administration before vaccination with Respiratory 
Syncytial virus was reported to lower humoral responses, but not cellular immunity. This matter 
can be investigated as part of clinical trial by measuring immune responses on they who exposed 
and treated with convalescent plasma to prevent disease. If the risk was proven to be real, these 
people can be vaccinated with COVID-19 when vaccine available.  
 
Recipients’ risk relate with blood plasma transfusion include immunologic / allergic reaction 
towards blood plasma. The most severe risk that might happen to recipients is TRALI (transfusion-
related acute lung injury). Risk of TRALI can be decreased by better plasma processing with 
extracting donors’ plasma using plasmapheresis process. Meanwhile, anaphylactic shock still can 
happen even though very rare.  
 
Managements for decreasing risks starting from donor election, donor’s blood extraction, plasma 
processing which also decrease the risk of blood-transmission infectious disease, storing 
process, and administration process of convalescent plasma which follows valid standard 
regarding blood plasma transfusion.  
 
Several available historical data up to this moment regarding convalescent plasma shows that 
this therapy is safe for COVID-19 patients. Thus, with high number of deaths caused by COVID-
19 especially on elder patients and vulnerable one, the benefit of this therapy is greater than the 
risk for vulnerable patients or patients with progressing early stage.  However, for every cases 
which convalescent plasma therapy is considered, assesment of rish and benefit will be done to 
evaluate individual variables. This consideration has been submitted recently with decision to use 
mAb in Ebola virus treatment.    
 
Direct benefit that can be felt by patients is improvement of health status which from severe stage 
at the beginning convert to well condition and shorten hospitalization period.  
 
B. 
Summary of References : 
 
1. Summary of previous studies according to research topic, including unpublished one which 
acknowledged by researchers & sponsors; and published research informations, including if 
animal studies available. One page maximum (p5) – G4.  
 
Evidences showed that convalescent plasma from COVID-19 survivors can be used for 
treatment without severe adverse effects. Thus, it might be useful to examine its safety and 
efficacy of convalescent plasma transfusion on SARS-CoV-2 patients. Challenges in 
convalescent plasma therapy are availability of enough donor, clinical condition, virus kinetic, 
and interaction of host and SARS-CoV-2 which has to be explained before considering 
convalescent plasma as choice of therapy.  
 
There is an urgent need to decide new therapy for treating severe clinical condition. Hopefully 
it may lessen deaths, reduce virus spreading and decrease potential of pandemic in the future. 
Even though currently researchers are developing prevention and specific therapy in 
vaccinology, monoclonal antibody, peptides, interferon and small molecule medicines to fight 
SARS-CoV-2; development process still takes few more months to test in-vitro / in-vivo 
efficacy and also depends on result of its clinical trial.  

 
6 
      
Open-label randomized clinical trial from antiviral therapy was reported recently. In this 
research, 199 patients was allocated randomly using antiviral agent lopinavir – ritonavir or 
treatment standard; this regimen was tested not effective. One of the reasons might be 
because of registered patients already on IIb stadium (hypoxia stage). Virus pathogenicity 
may just 1 dominant aspect from overall pathophysiology and patient’s inflammatory 
responses as the main pathophysiology.3–5  
 
Symptomatic COVID-19 patients varied from mild until critical; most infection is not severe. 
Confirmed infected patient has 3 phases of disease severity:7 
 
1. Mild ( No pneumonia or mild one ) was reported in 81% cases  
2. Severe (example, with dyspnea, hypoxia, or >50% lung involvement on lung imaging in   
24 – 48 hours) was reported in 14% cases.  
3.  Critical (example, respiratory failure, shock of multi-organ dysfunction) was reported in 
5% cases.  
 
Experience from previous pandemics like SARS-CoV-1 showed that convalescent plasma 
contain antibody that might have neutralizing effect towards relevant virus. On SARS-CoV-2 
case, possible mechanism if this therapy was applied is protection arise from neutralized 
virus by antibody that contained in transfused plasma. However, there might be another 
possible mechanism such as ADCC (antibody-dependent cellular cytotoxicity) response 
and/or phagocytosis.8 
 
A protocol for convalescent plasma usage in Corona virus Middle East syndrome was made 
in 2012. One possible explanation for efficacy of convalescent plasma therapy is antibody 
from convalescent plasma can suppress viremia. Schoofs et.al reported that immunotherapy 
which mediated by 3BNC117 (broad neutralizing antibody towards HIV-1) increase humoral 
immunity towards HIV-1.  
 
In-vivo experiments also showed that this antibody effect not only limited in virus clearance 
and blockage new infection, but also increase clearance of infected cells. Peak of viremia 
happens on first week of infection in most virus disease. Patients usually develop primary 
immune response on day 10th – 14th, which followed by virus clearance. Thus, theoretically, 
convalescent plasma therapy is more effective to be given in early stage of disease. But, 
other treatment may give effect on relationship between convalescent plasma and level of 
antibody, including antiviral, steroid, & intravenous immunoglobulin.  
 
Spectrum of symptomatic infection varied from mild until critical; most cases is not severe.   
 
Stadium I (Mild) – Early Infection :3–5 
 
Early stage happens when virus inoculate to human body and beginning of disease 
process. Generally, this stage involve incubation period which related with mild and 
unspecific symptoms like malaise, fever and dry cough. During this period, SARS-CoV-2 
replicate, like building place to live inside the host especially focusing in respiratory 
system.  
 

 
7 
Like their older relatives, SARS-COV (which responsible for SARDS pandemic 2002-
2003) bind its target using ACE-2 (Angiotensin Converting Enzyme) receptors on human 
cells. A lot of ACE-2 receptors located on human lung, intestine epithelial, and vessels 
endothelial. As result of transmission process through air and affinity towards lung ACE-2 
receptors, infection usually appears with mild respiratory and systemic symptoms.  
 
Diagnosing Stadium I (Parameter):  
• 
Positive PCR result from respiratory sample  
• 
IgG and IgM SARS-CoV-2 serum testing, with  
• 
Lung CT Scan ,  
• 
Complete blood count (CBC) and liver function test. CBC only reveal lymphopenia and 
neutrophilia without other significant abnormalities.  
 
Treatment of Stadium I:  
• 
Main objective : eliminate symptoms  
• 
If proper antiviral (like Remdesivir ) was proven to be effective, patients’ treatment 
targets are decreasing symptoms duration, minimizing transmission and preventing 
disease progression.  
• 
If patient can limit the disease severity only up to stadium I, the prognosis and recovery 
will be very good.  
 
Stadium II (Moderate) – Lung Involvement (Phase IIa – without hypoxia & Phase IIb 
– with hypoxia):3–5 
 
Diagnosing Stadium II :  
• 
CT imaging showed diffuse lung involvement; the principle are virus multiplication and 
lung local inflammation.  
• 
Patient develops viral pneumonia; with cough, fever, and possibility of hypoxia (defined 
as PaO2/FiO2 <300 mmHg) 
• 
Imaging with CT-Scan and thorax x-ray reveal bilateral infiltrates or ground-glass 
opacity.  
• 
Blood test showed severe lymphopenia, along with elevation liver function test.  
• 
Systemic inflammation marker may elevate but not significantly.  
• 
Most patients with COVID-19 Stadium II need to be hospitalized for observation and 
accurate management.  
 
Treatment of Stadium II: 
• 
Main treatment includes supportive cares and available antiviral therapy like Remdesivir  
• 
In most Pneumonia COVID-19 cases, procalcitonin serum level ranged from low until 
normal.  
• 
On early stadium II (without significant hypoxia), avoid corticosteroid usage.  
• 
In situation when hypoxia occur, there is possibility that mechanical ventilation will be 
needed.  
• 
Anti-inflammation therapy usage like corticosteroid might be helpful and can be used 
wisely.  
• 
Thus, Stadium II need to be divided with IIa phase (without hypoxia) and IIb phase (with 
hypoxia)  

 
8 
 
Stadium II (Critical) – Systemic Hyperinflammation 3–5: 
 
Small percentage of COVID-19 patients will progress to Stadium III (critical):  
• 
Manifested as non-lung systemic hyper-inflammation syndrome.  
• 
Systemic inflammation markers increase apparently  
• 
T-helper, T-cell suppressor and T-cell regulator decrease.  
• 
Cytokines and inflammation biomarkers such as IL-2, IL-6, IL-7, granulocyte colony-
stimulating factor, macrophage inflammation protein 1-α, tumor necrosis factor- α, C-
reactive protein, ferritin and D –dimer increase significantly on more severe patient.  
• 
Troponin and NT-pro BNP (N-terminal pro-brain natriuretic peptide) might be increase.  
• 
HLH (haemophagocytic lymphohistiocytosis)-like form might happens.  
• 
Vasoplegic shock, respiratory failure and even cardiopulmonary collapse can be seen in 
this stadium.  
• 
Systemic organs involvement, even myocarditis will manifest during this stadium.  
 
Treatment of Stadium III:  
• 
Depending on immunomodulatory agent usage to decrease systemic inflammation before 
producing multi-organ dysfunction.  
• 
Corticosteroid can be given along with cytokines inhibitor like Tocilizumab (IL-inhibitor) or 
Anakinra (IL-1 receptors antagonist) 
• 
Intravenous immunoglobulin (IVIG) plays a role in modulating immune system which under 
hyper-inflammation condition.  
• 
Overall, prognosis and recovery of critical stadium very poor and therapy would possibly 
improve the outcome 
 
Open-label randomized controlled trial from antiviral therapy just reported recently. In this 
trial, 100 patients was allocated randomly to antiviral agent lopinavir-ritonavir or treatment 
standard; this regimen was found not effective.  
 
One of the reasons might be because of registered patients already on IIb stadium 
(hypoxia stage). Virus pathogenicity may just 1 dominant aspect from overall 
pathophysiology and patient’s inflammatory responses as the main pathophysiology 
 
C. 
Field Conditions  
1. Brief description regarding research location ( please look P-2)  
 
a) Donor recruitment from COVID-19 survivors. Blood Transfusion Unit of Gatot Soebroto 
Indonesia Army Central Hospital isolates blood plasma from donor then examines the 
plasma for blood type & pathogens contained.  
b) Examining convalescent plasma for antibody neutralizing act by in-vitro towards SARS-
CoV-2 culture (Done at Eijkman Institute)  
c) Testing level of antibody in convalescent plasma (Done at Bio Farma – Government 
Corporate)  
 
Information regarding availability of eligible facility for save and precise research:  
Bio Farma has production facilities which certified with Good Manufacturing Practice.  

 
9 
 
Demographic / Epidemiologic Information which relevant with research location:  
Plasma extraction will be done in Jakarta at Gatot Soebroto Indonesia Army Central Hospital.  
Meanwhile, plasma development process to be end product will be done at Bio Farma in 
Bandung.  
 
 
 
 
D. 
Research Design  
 
1. Research objectives, hypothesis, research questions, assumption and research 
variables (P-1; S-1,2) 
 
Research objectives:  
1) Producing a good quality convalescent plasma from COVID-19 survivors, and   
2) Assess the safety of serial convalescent plasma transfusion in severe stage COVID-19 
 
Proposed hypothesis is convalescent plasma administration is safe and possibly improve 
clinical outcome of severe stage COVID-19 patients.  
 
Proposed research questions  
1) Does plasma from COVID-19 survivors can neutralize virus during in-vitro examination 
and produce good quality convalescent plasma?  
2) Does convalescent plasma from COVID-19 survivors safe and could possibly produce 
better recovery, better prognosis and heal COVID-19?  
 
Research variables:  
1) Progression / improvement of clinical symptoms : fever, cough, breathing difficulty, chest 
pain, sore throat, nausea, vomit, diarrhea, anosmia, erythema, conjunctivitis, ILI 
(influenza-like illness).  
2) Progression/Improvement of lung lesion from lung imaging.  
3) Progression/Improvement of routine laboratory test criteria: CRP, procalcitonin, 
Complete blood count, leukocyte count, leukocyte differential count, SGOT, SGPT, 
blood gas analysis, ureum, creatinine, e-GFR, blood glucose.  
 
  
2. Detail description of Research Design  
 
This research is an interventional experimental study by evaluating prospectively before and after 
convalescent plasma administration on COVID-19 patients. There are 2 groups (phase) consist 
of donor and recipient group.  
 
Donor group consists of mild COVID-19 survivors. Donor eligibility criteria : 1) Positive history of 
COVID-19 which already declared healthy, 2) 14-28 days after recovery or 14 days after repeated 
negative nasopharyngeal swab, 3) Negative PCR result, 4) Male / female donor which free from 
HIV, Hepatitis B & Hepatitis C, 5) Signing informed consent form for COVID-19 Survivors Plasma 
Donor  
 
Recipient group consists of severe COVID-19 patients which still hospitalized.  

 
10
 
Donor is COVID-19 survivors with inclusion criteria as follows:  
1. 
Age: ≥ 18 until ≤ 60 years old  
2. 
Complete resolution of symptoms for minimum 14 days before plasma donation or 14 days 
after repeated negative nasopharyngeal swab.  
3. 
Donor has been declared negative from twice nasopharyngeal swab.  
4. 
Positive history of hospitalization with mild symptom of COVID-19 or independent self-
isolation with mild symptoms COVID-19 and already confirmed with RT-PCR (Real Time-
Polymerase Chain Reaction)  
5. 
Female donor candidate not is not pregnant (negative result of serum pregnancy test). HLA 
examination was done if pregnancy history was positive previously. Female with negative 
pregnancy history more prioritized.  
6. 
Approving NAT (Neutralizing Antibody Titers) examination. If NAT examination can be 
done before transfusion, optimal titer which greater than 1:80 is more preferred.  
 
 
Blood Transfusion Unit will classify donor candidates who fulfill criteria as follows:  
1. Blood type (ABO) and Rhesus (RhD) identification.  
2. Blood screening towards HIV, HBV, HCV, syphilis and other infections which considered 
necessary using immunoassay method and / NAT if possible.  
3. Hemoglobin level examination  
4. If possible, titration of total COVID-19 antibody and COVID-19 neutralizing antibody might 
help donor qualification, especially if donor willing to donate their plasma continuously.  
5. Erythrocyte antibody screening examination, if possible.  
 
Recruited recipients are they who fulfill inclusion and exclusion criteria as follows: 3,4, 8,9, 
17,23 
 
Recipient inclusion criteria:  
1. Age : ≥ 18 until ≤ 60 years old 
2. Confirmed case with RT-PCR from nasopharyngeal swab.  
3. Classified as severe COVID-19  
•   Severe COVID-19 fulfill at least one condition below:  
o Breathing difficulty or severe pneumonia treated supportively with quick progressivity 
and high viral load 
o Respiratory rate >30 times/minute  
o Blood oxygen saturation <93% or with PaO2/FiO2 <300 (PaO2 measured in mmHg 
and FiO2 measured as inspired oxygen fraction)  
o Arterial PF ratio < 300 and/or lung infiltrate >50% in 24-48 hours.  
o Not yet or already supported with mechanical ventilation  
4. Hospitalized severe stage COVID-19 patients with comorbidities will be given immediately.   
 
Recipient exclusion criteria:  
1. Pregnant patient 
2. Having contraindication towards transfusion or any history of cross reaction previously towards 
blood product transfusion.  
 
Donor’s convalescent plasma is extracted from subjects who fulfil inclusion criteria.Ten ml 
serology sample is extracted for Blood Transfusion Unit of Gatot Soebroto Indonesia Army Central 
Hospital. Another 200 ml plasma is extracted using apheresis method which will be divided into 2 
bags @100 ml then it will be tested for blood type & pathogen. Antibody titer examination was 

 
11
done using 2 ml sample at Bio Farma and neutralizing test using 3 ml sample was done at Eikjman 
Institute. 
In urgent condition, plasma can be transfused to COVID-19 patients before 6 hours. In not urgent 
condition, plasma can be kept at -70oC degree so it turns to 200 ml frozen plasma. If the plasma 
will be used, thawing done at 30-37oC then it can be transfused to COVID-19 patients before 6 
hours.  
  
Disease Severity Spectrum  
Basic for Timing of  COVID-19 Convalescent Plasma Therapy 
 
Cited from7 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
12
In Vitro Protocol 
• 
Ethical clearance proposal ( Gatot Soebroto Hospital ) 
• 
Plasma extraction Gatot Soebroto Blood Transfusion Unit 
• 
Neutralizing examination ( Eijkman Institute ) 
• 
Convalescent Plasma Development Process (Bio Farma)
In Vivo Protocol 
• 
Validated convalescent plasma process  
• 
Finalization of In-Vivo protocol (Bio Farma & Gatot Soebroto)  
• 
Ethical clearance proposal (Gatot Soebroto Hospital) 
• 
Submission of Clinical Trial Approval to BPOM
Anti COVID-19 Convalescent Plasma Development Divided in 2 Stages 
 
 
Research and convalescent plasma therapy development divide into 2 activites which are in-vivo 
experiment ( intervention to observe overall effects towards COVID-19 positive subjects ) then in 
parallel, in-vitro experiment ( convalescent plasma effect on neutralizing virus ). Safety and 
efficacy of convalescent plasma will be observed in severe stage COVID-19 patients which 
hospitalized.  
 
In-vivo research – plasma which already pass quality control used in COVID-19 patient. Its safety 
and efficacy towards hospitalized severe stage COVID-19 patients was observed, then in parallel 
in-vitro research is done. In-vitro research including donor election, plasma characterization, virus 
inactivation, and efficacy testing of plasma until it is declared pass quality control.  
 
Refinement process during this in-vitro research involving Blood Transfusion Unit at Gatot 
Soebroto Indonesian Army Central Hospital; examination towards SARS-CoV-2 culture was done 
at Eijkman Institute, meanwhile evaluation of convalescent plasma antibody level was done by 
Bio Farma. Process sequence in this stage is by drawing COVID-19 survivors’ plasma donor in 
amount 200 ml. Then virus deletion was done and the plasma was given to severe COVID-19 
patients. More plasma donor from COVID-19 survivors will increase data which collected and 
analyzed.  
 
Measured variables:  
 
1. Progression / improvement of clinical symptoms : fever, cough, breathing difficulty, chest 
pain, sore throat, nausea, vomit, diarrhea, anosmia, erythema, conjunctivitis, ILI (influenza-
like illness).  
 
2.    Improvement of lung lesion from lung imaging 
 
3.    Improvement of routine laboratory test criteria: CRP, procalcitonin, complete blood count, 
SGOT, SGPT, blood gas analysis, ureum, creatinine, e-GFR, blood glucose, D-dimer, IL-1, IL-6 
and IL-8. 
 
 
 
 
 
 
 
 

 
13
COVID-19 Plasma Apheresis Research Plot  
 
Donor (COVID-19 Survivors)
10 mL sample serology extraction for 
Gatot Soebroto Blood Transfusion Unit 
Plasma volume : 200 ml/bag
200 mL frozen plasma
Transfuse to COVID-19 
patient before 6 hours 
Transfuse to COVID-19 
patient before 6 hours 
3 mL sample serology extraction for 
antibody titer examination at Bio Farma 
3 mL sample serology extraction for  
neutralization examination at Eijkman 
• 
200 ml plasma extraction using 
apheresis method
• 
Blood type & pathogen screening
Urgent condition
Not urgent condition
Kept at -70oC
Thawing process at 30-37oC
 
 
 
3. If clinical trial, description has to include whether treatment group is allocated randomly or nor 
(including randomization method) P5-21 and whether it is blinded or not. ( If not clinical trial, 
it is enough to write : irrelevant)(p12)  
 
Irrelevant  
 
Sampling  
1. Number of subject needed according research objectives and its calculation based on 
statistic.  
 
Sample number needed ranged from 5 – 10 subjects ( amended ) in each treatment group (mild 
and severe stage). This sample is an early study. Analysis of this trial use T-test independent 
which is comparative test or comparison test to know whether if there is any significant mean 
difference between 2 interval data groups. Two independent groups described earlier is 2 
unpaired groups which means source of data come from different source.   
 
 
 
 
 
 
 

 
14
 
4. Participant / subject criteria and exclusion / inclusion justification (P-3)  
 
 
Donor is COVID19 – survivors (COVID-19 patients whom already declared healthy) with 
inclusion criteria as follows:  
1. Age: ≥ 18 until ≤ 60 years old 
2.Complete resolution of symptoms for minimum 14 days before plasma donation or 14 days after 
repeated negative nasopharyngeal swab. 
3.Donor has been declared negative from twice nasopharyngeal swab 
4. Positive history of hospitalization with mild symptom of COVID-19 or independent self-isolation 
with mild symptoms COVID-19 and already confirmed with RT-PCR (Real Time-Polymerase 
Chain Reaction) 
5. Female donor candidate not is not pregnant (negative result of serum pregnancy test 
 
Blood Transfusion Unit then will classify donor candidates who fulfill criteria as follows:  
1. Blood type (ABO) and Rhesus (RhD) identification.  
2. Blood screening towards HIV, HBV, HCV, syphilis and other infections which considered 
necessary using immunoassay method and / NAT if possible.  
3. Hemoglobin level examination  
4. Erythrocyte antibody screening examination, if possible. 
 
Recruited recipients are they who fulfill inclusion and exclusion criteria as follows: 3,4, 8,9, 17,23 
 
Recipient inclusion criteria:  
1. Age: ≥ 18 until ≤ 60 years old 
2. Confirmed case with RT-PCR from nasopharyngeal swab.  
3. Classified as severe COVID-19  
• 
Severe COVID-19 fulfill at least one condition below:  
o Breathing difficulty or severe pneumonia treated supportively with quick progressivity 
and high viral load 
o Respiratory rate >30 times/minute  
o Blood oxygen saturation <93% or with PaO2/FiO2 <300 (PaO2 measured in mmHg 
and FiO2 measured as inspired oxygen fraction)  
o Arterial PF ratio < 300 and/or lung infiltrate >50% in 24-48 hours.  
o Not yet or already supported with mechanical ventilation  
4.Hospitalized severe stage COVID-19 patients with comorbidities will be given immediately.   
 
 
Recipient exclusion criteria:  
1. Patient in pregnant condition  
2. Having contraindication towards transfusion or any history of cross reaction previously towards 
blood product transfusion. 
 
 
Donor’s convalescent plasma is extracted from subjects who fulfil inclusion criteria. Ten ml 
serology sample is extracted for Blood Transfusion Unit of Gatot Soebroto Indonesia Army Central 
Hospital. Another 200 ml plasma is extracted using apheresis method which will be divided into 2 
bags @100 ml then it will be tested for blood type & pathogen. Antibody titer examination was 
done using 2 ml sample at Bio Farma and neutralizing test using 3 ml sample was done at Eikjman 
Institute. 

 
15
In urgent condition, plasma can be transfused to COVID-19 patients before 6 hours. In not urgent 
condition, plasma can be kept at -70oC degree so it turns to 200 ml frozen plasma. If the plasma 
will be used, thawing done at 30-37oC then it can be transfused to COVID-19 patients before 6 
hours.  
 
 
5. Vulnerable group sampling : Reason to involve pediatric patients or adult patients who not 
capable to give agreement after explanation of vulnerable group, and preventive 
measurement if the risks happen. (P-15 until 19)(p15) 
 
This research does not involve pediatric or adult patients who unable to give approval after 
explanation.  
 
Intervention ( For qualitative secondary data data user, enough to write “irrelevant” then 
proceed to “benefit” ) 
Description and explanation of all interventions (treatment administration methods, including 
administration route, dosage, dosage interval, and treatment duration of usable product) 
 
In this intervention research, 5 – 10 patients will be recruited. Subject will be given 100 ml 
convalescent plasma on day 0, 3, 6 which originated from COVID-19 donor (healthy condition 
with antibody neutralizing titer ≥ 1/80) as additional treatment. Early justification is safety of 
convalescent plasma transfusion and secondary justification is clinical symptoms improvement 
and laboratory parameters within 3-5 days after transfusion.  
 
 
6. Plan and justification to continue or stop treatment standard during trial (p4 and 5)  
 
Research will be stopped if recipient suffer from serious adverse effects such as TRALI, 
anaphylactic shock.  
 
 
7. Another treatment that might be given/allowed or becoming contraindication during trial.  
 
In this trial, patient already treated with medication:  
▪ 
Azithromycin 500 mg/24H IV (5 – 10 days)  
▪ 
Chloroquine 500 mg/12H (5-10 days) or 
Hydroxychloroquine 200 mg/12H (5-10 days)  
*) Note: If electrocardiogram show abnormal result, it is contraindication for 
Chloroquine or Hydroxychloroquine (Cardiologist will be consulted) 
▪ 
Methisoprinol 100 mg/kgBW/day (divided in 4 dosage)  
▪ 
Multivitamins which contain Zinc and Vitamin C. For example :  
Surbex Z 1 tab/12H, or Seloxy AA 1 tab/12H  
▪ 
Cernevit 1 vial/24H (3 days) 
▪ 
Omeprazole injection 40 mg/24H  
▪ 
Intravenous fluid drops : Crystalloid solution  
▪ 
If breathing difficulty (+), oral bronchodilator will be given.  
▪ 
Mucolitic / Expectorant: Fluimucyl 600 mg/12H effervescent tab.  
▪ 
Antipyretic if fever  
▪ 
Hepatoprotector if there is abnormal liver function  
 
 

 
16
8. Other clinical or laboratory test which is necessary to be done  
 
Laboratory data including white blood cell count, lymphocyte count, chemical parameter which 
evaluate liver and renal function, cycle threshold point, inflammation factor C-reactive protein 
(CRP), procalcitonin, lung imaging test.  
 

 
17
 
E. 
Outcome Monitoring  
1. Sample from standardized case report form, recording method of therapeutic response 
(description, evaluation method and measurement frequency),follow-up procedure, and if 
possible, proposed measurement to define subject compliance who receive the treatment 
(see appendix)(p17)  
 
Measured variables:  
 
1. Progression / improvement of clinical symptoms : fever, cough, breathing difficulty, chest 
pain, sore throat, nausea, vomit, diarrhea, anosmia, erythema, conjunctivitis, ILI (influenza-
like illness) on day 1 
2. ,4,7 and 14 after convalescent plasma administration  
 
 
3. Improvement of lung lesion from lung imaging on day 1, 4, 7 and 28 after first convalescent 
plasma administration.  
 
4. Improvement of routine laboratory test criteria: CRP, procalcitonin, complete blood count, 
SGOT, SGPT, blood gas analysis, ureum, creatinine, e-GFR,blood glucose, D-Dimer, IL-
1, IL-6 and IL-8 on day 1,4,7 and 14 after first convalescent plasma administration. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
18
 
 
 
 
 
 
 
BLOOD EXAMINATION RESULT TABLE of RESEARCH SUBJECT  
 
Patient Name 
: 
Gender  
: M / F 
Date of Birth 
: 
Address 
: 
Medical Record Number: 
 
 
Type of  
Examination 
Result 
Examination before 
Convalescent Plasma 
 
Date................................. 
Day 
1 
After 
Convalescent 
Plasma  
Date........................ 
Day 3 After 
Convalescent Plasma  
 
Date................................. 
Day 6 After 
Convalescent Plasma  
 
Date................................. 
Clinical 
symptoms  
 
 
 
 
Laboratory 
parameter : 
 
-CRP 
-PCT 
-CBC 
-SGOT 
-SGPT 
-Blood gas 
analysis 
-Ureum 
-Creatinin 
-e-GFR 
-Blood 
glucose 
-D-dimer 
 
Biomarkers: 
-IL1,IL,IL8 
 
 
 
 
Lung imaging 
parameter  
 
 
 
 
 
Examiner, 
 
 
 
 
(..................................) 
Examiner, 
 
 
 
 
(..................................) 
Examiner, 
 
 
 
 
(..................................) 
Examiner, 
 
 
 
 
(..................................) 
 
 
 
 

 
19
F. 
Termination of Research and Its Rationale 
1. Rule and criteria when subject can be terminated from research/clinical trial or in multi-centre 
trial, when a centre / institution can be deactivated, and when the trial can be terminated (not 
to be continued)  
 
Convalescent plasma administration is stopped if subject suffer risk related with blood plasma 
transfusion, including immunologic / allergic reactions towards blood plasma. The most severe 
risk that might happen to recipients is TRALI (transfusion-related acute lung injury). Risk of TRALI 
can be decreased by better plasma processing with extracting donors’ plasma using 
plasmapheresis process. Meanwhile, anaphylactic shock still can happen even though very rare. 
Mild adverse effects which might happen are fever and arise of purpura.  
 
 
 
G. 
Adverse Event and Complication ( Unexpected Event )  
Recording and reporting adverse events / reactions, and complication handling requirement (P-
4, 6)  
  
Format attached  
 
1. Risks known from adverse events, including risk related with each intervention plan and 
related with medicine, vaccine or procedure that will be tested. (P-4, 5)  
 
Before convalescent plasma administered to subject, informed consent was done towards patient 
/ family regarding adverse effect risk, disease prognosis and measurement action that if adverse 
events happen. The most severe adverse effect might happen is TRALI (transfusion-related acute 
lung injury) with incidence rate 1:5.000 and also anaphylactic shock even though very rare. Mild 
adverse effects which might happen are fever and arise of purpura. 
 
 
H. 
Complication Handling (p-14) 
Detail plan if there is risk more than minimal risk / physical wound, make detail plan, insurance 
availability, treatment facility / medical fee availability. Compensation if disability / death happen.  
 
If adverse effect arise, then subject will be hospitalized at hospital and become responsibility of 
researcher team and hospital.  
 
Management for minimize risks starting from donor election, donor sampling, plasma processing 
including minimize risk of blood-transmission contagious infection, storing process, labelling 
process, transporting plasma from Blood Transfusion Unit Gatot Soebroto Indonesia Army 
Central hospital to ward; dosage and how administer convalescent plasma following valid 
standard of blood plasma transfusion.  
 
I. 
Benefits  
1. Personal benefit of research to subject and others (P-4)  
 
• 
Benefit for Donor: Donating their blood plasma as contribution for humanity in developing 
convalescent plasma therapy to save other lives.  
• 
Benefit for others / COVID-19 patients: One step forward of treatment availability to heal / 
save COVID-19 patients’ life and shorten hospitalization period.  

 
20
 
2. Research benefits for population including new knowledge which resulted from trial (P-1, 4)  
 
For Population  
This trial outcome can help availability of anti COVID-19 convalescent plasma product where 
this therapy give benefits such as:  
• 
Finding method to process convalescent plasma from COVID-19 patients  
• 
Providing convalescent plasma material for further testing which is efficacy test towards 
patient if the development succeed. There will be another further trial regarding this 
matter.  
 
For science  
• 
Providing information for basic knowledge to develop COVID-19 convalescent plasma in 
Indonesia 
• 
As national even international publication materials  
 
 
J. 
Sustainability of Benefits Guarantee (p28) 
1. Possibility of continuity access if intervention outcome produces significant benefits, 
available modality, available parties who need treatment continuity, organization who will 
pay the expenses, and duration (P-6, 14) 
 
 

 
21
 Specimen guarantee – In not urgent condition, plasma can be stored at -70oC degree so 
it will convert to 200 ml frozen plasma for a year and can be administered to other patient 
in other research centre. Storage will be set at -70oC and locked; it only can be accessed 
by authorized staff.  
 
K. 
Informed Consent  
1. Proposed method to gain informed consent and planned procedure to communicate 
research information to subject candidates including name and guardian position for those 
who unable to give consent. (P-9)  
 
Informed consent is delivered to donor and recipient with persuasion and explanation 
regarding benefits and objectives of research.  
 
 
3. For pregnant woman : Available planning to observe mother and child health for short and 
long term. (P-14, 19)  
 
         Irrelevant, pregnant woman is not allowed to donor  
 
 
L. 
Guardian (p-10, 16,17)  
1. Presence of legal guardian if subject candidate unable to give informed consent (P-10, 
16, 17 )   
 
There will be request for valid legal guardian if patient unable to give consent after 
explanation; but for donor, donor consent is more preferred.  
 
4. Presence of parents or guardian if children understand the informed consent but not reach 
legal age to make decision  
        
Irrelevant  
 
M. 
Persuasion  
1. Description of persuasion / incentive to subject candidate for participating such as money, 
gift, free service or others. (P-13)  
 
 
Both donor and recipient as subject independently decide whether will participate or not. 
If donor eligibility criteria is not fulfilled, subject will be informed by physician in charge at 
our Blood Transfusion Unit. Donor will receive package that consist of milk, vitamin and 
biscuits as gratitude.  
 
 
5. Plan, procedure and person in charge to inform participant’s benefits and risks ; or regarding 
other research with same topic which can influence continuity subject participation during trial 
(P-9)(p33)  
 
Donor requirement information will be informed by Blood Transfusion Unit Gatot Soebroto 
Indonesia Army Central Hospital staff  
 
 

 
22
Please contact us at Blood Transfusion Unit Gatot Soebroto Indonesia Army Central 
Hospital: 
 
a. Dwi Novianingtyas, Clinical Pathologist, MD / 0821.1228.7478 / dwinovinobi@gmail.com 
b. Jenie Erawati Muchti, M.Ked (Clin.Path), Clinical Pathologist, MD / 0813.1484.2822 / 
muchti.jea@gmail.com 
 
 
6. Planning to inform research outcomes to subject or participant (P-24)  
 
N. 
Confidentiality  
2. Recruitment process (for example through advertisement); and steps to keep privacy and 
confidentiality during recruitment (P-3)  
 
Donor’s name and identity will be classified  
 
7. Protection steps for keeping private data confidential and respecting people privacy including 
caution to prevent leakage of confidential family genetic test result except permitted by 
relevant one.  
 
Information which delivered to Bio Farma only blood type and time of sampling; no 
information regarding donor identity. Thus, patient identity as subject will also be 
classified.  
 
 
8. Information about coding (if exist); to make subject’s identity, storing information (place, time 
and how) and also by whom the data can be opened if emergency happen. (P-11, 12)  
 
Coding technique for donor identity:  
Sample sequence number / 4 digits of medical record number / date / month / COVID19-
RSPAD/2020 
 
Coding technique for recipient identity:  
Sample sequence number / 4 digits of medical record number / date / month / COVID19-
RSPAD/2020  
 
9. Possibility for further usage of personal data or biological material  
 
None  
 
O. 
Analysis Planning  
1. Description regarding statistic analysis plans, including intern analysis plan if needed, and 
criteria if or under which condition whole research will be terminated prematurely.  
 
This sample is an early stage of trial. Trial analysis use T-dependent test which is comparative 
test or difference test to know whether any significant mean difference according normal 
curve. If data distribution is abnormal, then analysis use Wilcoxon signed rank test.  
 
 
 
 
 

 
23
P. 
Safety Monitoring  
1. Planning to monitor continuity of medicine safety or other intervention which done in the trial; 
and if needed, independent committee establishment for data and safety monitoring (P-4).  
 
Recipient monitoring:  
1. Progression / improvement of clinical symptoms : fever, cough, breathing difficulty, chest pain, 
sore throat, nausea, vomit, diarrhea, anosmia, erythema, conjunctivitis, ILI (influenza-like 
illness) 
2. Improvement of lung lesion from lung imaging 
3. Improvement of  routine laboratory test criteria : CRP, procalcitonin, complete blood count, 
SGOT, SGPT, blood gas analysis, ureum, creatinine, e-GFR,blood glucose, white blood cell 
count  
 
 
Specimen guarantee which is storage place set at -70oC degree, locked and only can be 
accessed by authorized staff.  
 
All the adverse event and severe adverse event will be reported to responsible ethics committee 
within 24 hours since the event took place (SAE). 
 
This research is monitored by appointed KEPPK team.  
 
 
Q. 
Conflict of Interest  
1. Regulation to resolve financial / other conflicts which could influence researcher / other staff 
decision ; informing it to institution committe regarding possible conflict interest; committe 
communicate it to ethical committe and then communicate it to researcher regarding further 
steps which necessary to be done.  
 
This is a non-profit research  
 
 
R. 
Social Benefit  
For research which is done at poor resource, sponsor contribution for capacity building , scientific 
& ethic study; health research. Assurance that capacity building purpose according to expectation 
of participant and community where the research is done.  
 
 
10. Research protocol / document delivered to ethical committee including description of 
community involvement planning and it shows which resources allocated to involving activitity. 
The document describe what will be and has been done; when and by whom to ensure that 
population clearly mapped for simplify their involvement during research, to ensure that 
purpose of research  
 
Protocol attached  
 
 
S. 
Data Rights  
1. Especially if sponsor is private sector,legal contract which declared to whom publication right 
research result belong; and obligation for joint preparation and research outcome report draft 
is given to researcher. (P-24) (B dan H, S1,S7) 
 

 
24
Publication belongs collectively between Gatot Soebroto Indonesia Army Central Hospital, Bio 
Farma and Eijkman.  
 

 
25
 
T. 
Publication  
Planning of result publication on certain field ( such as epidemiology, genetic, sosiology) which 
has risk to be in contrary with community, population, family and certain ethnic benefit; minimalize 
harm of this group by keeping data confidentially during and after trial; and publish research trial 
by always considering their dignity  
 
Lancet  or Pubmed  
 
If the research result is negative, making sure that the result will be available through publication 
or by reporting it to drug administration authority. (P-24)  
  
If the result is negative, it will be reported to Bio Farma BoE, Gatot Soebroto Indonesia Army 
Central Hospital directors and it will be coordinated with Indonesia Health Ministry.  
 
U. 
Funding  
Resource and amount of research fund, sponsor institution, and financial commitment description 
from sponsor to research institution, researcher, research subjects, and if exist, to community (P-
25)  
 
Early research funding is supported by Bio Farma, Simultaneously, collaboration agreement is 
prepared between Bio Farma, Gatot Soebroto Indonesia Army Central Hospital and Eijkman 
Institute.  
 
 

 
26
 
 
V. 
Ethical Commitment  
11. Main researcher declaration that all principles written in this guideline will be obeyed. 
       
         Main researcher and other researchers will obey all principle that written in this guideline.  
 
12. (Track Record) History of previous ethic protocol proposal and its result ( content with title and 
date of research and ethical committe review result)  
 
None  
 
13. Declaration that if there is evidende of data fraud, it will be handled according to policy sponsor 
for taking necessary action.  
 
If there is evidence of data fraud, it will be handled according to sponsor policy for taking 
necessary action  
 
 
 
 
Main researcher signature  
Jakarta, April 4th  2020 
 
 
Marliana Sri Rejeki, Clinical Pathologist, MD  
 
 
 
 

 
27
W. 
References  
References list referred in protocol (p40):  
1. Shanmugaraj B., Siriwattananon K., Wangkanont K., Phoolcharoen W. Perspectives on 
monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 
(COVID-19). Asian Pac. J. Allergy Immunol. 38, (2020). 
2. Shen, C. et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. 
JAMA (2020) doi:10.1001/jama.2020.4783. 
3. Siddiqi, H. K. & Mehra, M. R. COVID-19 Illness in Native and Immunosuppressed States: A 
Clinical-Therapeutic 
Staging 
Proposal. 
J. 
Heart 
Lung 
Transplant. 
(2020) 
doi:10.1016/j.healun.2020.03.012. 
4. Casadevall, A. & Pirofski, L. The convalescent sera option for containing COVID-19. J. Clin. 
Invest. 130, 1545–1548 (2020). 
5. Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in 
Wuhan, China: a retrospective cohort study. The Lancet 395, 1054–1062 (2020). 
6. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, 
China. The Lancet 395, 497–506 (2020). 
7. McGoogan JM & Wu Z. Characteristics of and Important Lessons From the Coronavirus 
Disease 2019 (COVID-19) Outbreak in China Summary of a Report of 72 314 Cases From the 
Chinese Center for Disease Control and Prevention. JAMA E1–E4 (2020). 
8. Chen, L., Xiong, J., Bao, L. & Shi, Y. Convalescent plasma as a potential therapy for COVID-
19. Lancet Infect. Dis. 20, 398–400 (2020). 
9. Shen, C. et al. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma. 
JAMA - J. Am. Med. Assoc. 1–8 (2020) doi:10.1001/jama.2020.4783. 
10. 
Zhang, B. et al. Treatment with convalescent plasma for critically ill patients with SARS-
CoV-2 infection. Chest (2020) doi:10.1016/j.chest.2020.03.039. 
11. 
Duan, K. et al. The feasibility of convalescent plasma therapy in severe COVID-19 
patients: 
a 
pilot 
study. 
medRxiv 
2020.03.16.20036145 
(2020) 
doi:10.1101/2020.03.16.20036145. 

 
28
12. 
Revised Information for Investigational Covid-19 Convalescent Plasma. Investigational 
New drug (IND) and Devica Exemption (IDE) Process (CEBR). 
13. 
Tim TPK Covid-19 Indonesia. Penatalaksanaan Terapi Plasma Konvalesen bagi Pasien 
Covid-19. (2020). 
 
AB. 
Appendix  
 
1. Main Researcher Curriculum Vitae  
 
Researcher Team from Gatot Soebroto Hospital ( GS Hospital )  
No. 
Name 
Instituti
on 
Position in 
Team 
Job Description 
Information  
1 
Marliana Sri Rejeki, Clinical 
Pharmacologist, MD 
GS 
Hospital 
Main 
Researcher 
Responsible for report 
of all research technical 
activity at GS Hospital  
EL-GCP: 872/EL-
GCP/AKEPIN/2020 
2 
Familia Bela, Pathologic 
Anatomist, MD 
GS 
Hospital 
Researcher 
Responsible for report 
of all research technical 
activity at GS Hospital 
 
3 
Triono  Sundoro, MD 
GS 
Hospital 
Advisor 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
4. 
A. Budi Sulistya, 
Otolaryngologist, MD, 
MARS 
GS 
Hospital 
Advisor  
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
5 
Nana Sarmadi, Obstetric & 
Gynecologist, MD 
GS 
Hospital 
Supervisor 
and 
Research 
Coordinator 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
6. 
Dr. Agus Yunianto, Neuro 
Surgeon, MD 
GS 
Hospital 
Supervisor 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
7. 
Dr.Handrianto Setiajaya, 
Neuro Surgeon, MD 
GS 
Hospital 
Research 
Coordinator 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
8. 
Lukman Ma’ruf , Neuro 
Surgeon, MD, M.Kes., M.H 
GS 
Hospital 
Supervisor 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
9 
Retno Wihastuty, 
Pulmonologist, MD 
GS 
Hospital 
Researcher  
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
10. 
Ratna Andriyana, 
Pulmonologist, MD 
GS 
Hospital 
Researcher 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 

 
29
12. 
Martina Lily, Clinical 
Pathologist, MD 
GS 
Hospital 
Researcher 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
13 
 Dwi Novi, Clinical 
Pathologist, MD 
GS 
Hospital 
Researcher 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital 
 
14 
Jenie, Clinical Pathologist, 
MD 
GS 
Hospital 
Researcher 
Consultant and 
responsible for all 
research technical 
activity at GS Hospital  
 
15 
 
Wisvici Yosua Samin, 
Pediatrician, MD, M.Sc 
 
GS 
Hospital 
Researcher 
Responsible for report 
of all research technical 
activity at GS Hospital 
 
 
 
Researcher Team from PT. Bio Farma 
No. 
Name 
Institution 
Posision in 
Team 
Job Description 
1 
Dr. Neni Nurainy, 
Apt 
PT. Bio Farma 
(Persero) 
Main 
Researcher 
Responsible for all research 
technical activity at Bio Farma  
2 
Dr. Novilia Sjafri 
Bachtiar, MD., 
M.Kes 
PT. Bio Farma 
(Persero) 
Researcher 
Responsible for assisting all 
research technical activity at 
Bio Farma 
3 
Dyah Widhiastuti, 
MD, M.Kes 
PT. Bio Farma 
(Persero) 
Researcher 
Responsible for assisting all 
research technical activity at 
Bio Farma 
4 
Acep Riza 
Wijayadikusumah 
PhD 
PT. Bio Farma 
(Persero) 
Researcher 
Responsible for assisting all 
research technical activity at 
Bio Farma 
5 
Hidayat Setiaji 
MSc. 
PT. Bio Farma 
(Persero) 
Researcher 
Responsible for assisting all 
research technical activity at 
Bio Farma 
 
 
 
       Researcher Team from Eijkman 
 
No. 
Name 
Institution 
Position in 
Team 
Job Description 
1. 
Prof Dr Amin 
Soebandrio,MD, 
Internist  
Eijkman  
Researcher  
Responsible for assisting all 
research technical activity at 
Eijkman  
2 
Frilasita A Yudhaputri 
SSi. MBiomed. Sc Sisi 
Eijkman  
Main 
Researcher 
Responsible for assisting all 
research technical activity at 
Eijkman 
3. 
Prof Dr David Handoyo 
Mulyono, MD, Internist, 
Finasim 
Eijkman  
Researcher  
Responsible for assisting all 
research technical activity at 
Eijkman 
4.  
Dr. Tedjo Sasmono 
Eijkman  
Researcher 
Responsible for assisting all 
research technical activity at 
Eijkman 
 
 

 
30
2. Case Report Form Sample : Irrelevant  
 
 
* Sequence Number on CIOMS 2016 Guideline