Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome
Primary Purpose
COVID, Acute Respiratory Distress Syndrome
Status
Unknown status
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
Convalescent plasma
Standard of care
Sponsored by
About this trial
This is an interventional treatment trial for COVID
Eligibility Criteria
Inclusion Criteria:
- Patients aged more than equal to 18 years.
- COVID-19 confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR)
- Having severe pneumonia.
- PAO2 / FIO2 <300.
Exclusion Criteria:
- Contraindication to blood transfusions (fluid overload, history of anaphylaxis of blood products)
- Multiple and severe organ failure, hemodynamically unstable
- Other uncontrolled infections
- Disseminated intravascular coagulation (DIC) which requires a replacement factor/FFP
- Hemodialysis patients or CRRT (continuous renal replacement therapy)
- Active intracranial bleeding
- Significant myocardial ischemia
- Receiving tocilizumab treatment
Sites / Locations
- Dr. Cipto Mangunkusumo General HospitalRecruiting
- St. Carolus HospitalRecruiting
- Ciputra Hospital CitraRayaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
convalescent plasma and standard of care
standard of care
Arm Description
Outcomes
Primary Outcome Measures
All-cause mortality
Proportion of all-cause mortality
Secondary Outcome Measures
Length of stay in intensive care unit
Mean length of stay in intensive care unit
Duration of mechanical ventilation
Mean duration of mechanical ventilation
Body temperature (degree in Celsius)
Mean change from baseline using time series analysis
The Sequential Organ Failure Assessment (SOFA) Score
Mean change from baseline using time series analysis
PAO2/FIO2 ratio
Mean change from baseline using time series analysis
C-Reactive Protein (CRP) in mg/L
Mean change from baseline using time series analysis
D-Dimer in ng/mL
Mean change from baseline using time series analysis
Procalcitonin in ng/mL
Mean change from baseline using time series analysis
Interleukin 6 (IL-6) in pg/mL
Mean change from baseline using time series analysis
Allergic/ anaphylaxis transfusion reaction
Number of participants with allergic/ anaphylaxis transfusion reaction
Hemolytic transfusion reaction
Number of participants with Hemolytic transfusion reaction
Transfusion Related Acute Lung Injury
Number of participants with Transfusion Related Acute Lung Injury
Transfusion associated Circulatory Overload
Number of participants with Transfusion associated Circulatory Overload
Full Information
NCT ID
NCT04380935
First Posted
May 4, 2020
Last Updated
August 16, 2020
Sponsor
Indonesia University
Collaborators
Dr Cipto Mangunkusumo General Hospital, Fakultas Kedokteran Universitas Indonesia
1. Study Identification
Unique Protocol Identification Number
NCT04380935
Brief Title
Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome
Official Title
Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome in Referral Hospitals in Indonesia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 18, 2020 (Actual)
Primary Completion Date
October 31, 2020 (Anticipated)
Study Completion Date
October 31, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University
Collaborators
Dr Cipto Mangunkusumo General Hospital, Fakultas Kedokteran Universitas Indonesia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Corona virus disease 2019 (COVID-19) has been declared as a Pandemic by the World Health Organization (WHO). According to WHO report on March 31st 2020, globally COVID-19 have infected over 750,000 people and caused over 36,000 deaths with case fatality rate of 4.85%. In Indonesia, COVID-19 have infected 1,414 people and caused 122 deaths with case fatality rate of 8.63%. In severe cases, COVID-19 causes complications, such as acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ dysfunction syndrome (MODS), where age and comorbid illnesses as a major factor to these complications. Up to this point there are several promising therapies for COVID-19 but is not yet recommended and in need of further research. The use of convalescent plasma has been approved by the US Food and Drug Administration (FDA) through the scheme of emergency investigational new drug (eIND). This method has been used as the treatment in several outbreak or plague cases over the years, such as the flu epidemic in 1918, polio, measles, mumps, SARS (severe acute respiratory syndrome), EVD (Ebola virus disease) and MERS (middle-eastern respiratory syndrome) and this treatment shows better outcome. Several case report on the use of convalescent plasma for COVID-19 patients with ARDS and mechanical ventilation has been reported and shows promising outcome. Nevertheless, larger and multicenter research need to be done to assess and evaluate the effectiveness and safety of convalescent plasma therapy on for COVID-19 patients with ARDS.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, Acute Respiratory Distress Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
convalescent plasma and standard of care
Arm Type
Experimental
Arm Title
standard of care
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Convalescent plasma
Intervention Description
Convalescent plasma of recovered COVID-19 patients (donor)
Intervention Type
Drug
Intervention Name(s)
Standard of care
Intervention Description
According to national or hospital guidelines "COVID-19 Management Protocol"
Primary Outcome Measure Information:
Title
All-cause mortality
Description
Proportion of all-cause mortality
Time Frame
up to 28 days
Secondary Outcome Measure Information:
Title
Length of stay in intensive care unit
Description
Mean length of stay in intensive care unit
Time Frame
up to 28 days
Title
Duration of mechanical ventilation
Description
Mean duration of mechanical ventilation
Time Frame
up to 28 days
Title
Body temperature (degree in Celsius)
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
The Sequential Organ Failure Assessment (SOFA) Score
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
PAO2/FIO2 ratio
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
C-Reactive Protein (CRP) in mg/L
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
D-Dimer in ng/mL
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
Procalcitonin in ng/mL
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
Interleukin 6 (IL-6) in pg/mL
Description
Mean change from baseline using time series analysis
Time Frame
Day 1, 3, 5, and 7 after administration of therapy
Title
Allergic/ anaphylaxis transfusion reaction
Description
Number of participants with allergic/ anaphylaxis transfusion reaction
Time Frame
24 hours post-transfusion
Title
Hemolytic transfusion reaction
Description
Number of participants with Hemolytic transfusion reaction
Time Frame
24 hours post-transfusion
Title
Transfusion Related Acute Lung Injury
Description
Number of participants with Transfusion Related Acute Lung Injury
Time Frame
24 hours post-transfusion
Title
Transfusion associated Circulatory Overload
Description
Number of participants with Transfusion associated Circulatory Overload
Time Frame
24 hours post-transfusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged more than equal to 18 years.
COVID-19 confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR)
Having severe pneumonia.
PAO2 / FIO2 <300.
Exclusion Criteria:
Contraindication to blood transfusions (fluid overload, history of anaphylaxis of blood products)
Multiple and severe organ failure, hemodynamically unstable
Other uncontrolled infections
Disseminated intravascular coagulation (DIC) which requires a replacement factor/FFP
Hemodialysis patients or CRRT (continuous renal replacement therapy)
Active intracranial bleeding
Significant myocardial ischemia
Receiving tocilizumab treatment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Sinto, MD
Phone
+628158835432
Email
rsinto@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andri MT Lubis, MD, PhD
Organizational Affiliation
Faculty of Medicine Universitas Indonesia - Dr Cipto Mangunkusumo Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Dr. Cipto Mangunkusumo General Hospital
City
Jakarta
State/Province
DKI Jakarta
ZIP/Postal Code
10430
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Sinto, MD
Phone
+628158835432
Email
rsinto@yahoo.com
First Name & Middle Initial & Last Name & Degree
Andri MT Lubis, MD, PhD
First Name & Middle Initial & Last Name & Degree
Robert Sinto, MD
First Name & Middle Initial & Last Name & Degree
Elida Marpaung, MD, MBiomed
First Name & Middle Initial & Last Name & Degree
Cosphiadi Irawan, MD, PhD
First Name & Middle Initial & Last Name & Degree
Lugyanti Sukrisman, MD, PhD
First Name & Middle Initial & Last Name & Degree
Siti Rizny F Saldi, Pharm, MSc
First Name & Middle Initial & Last Name & Degree
William Djauhari, MD
Facility Name
St. Carolus Hospital
City
Jakarta
State/Province
DKI Jakarta
ZIP/Postal Code
10430
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Sinto, MD
Phone
+628158835432
Email
rsinto@yahoo.com
Facility Name
Ciputra Hospital CitraRaya
City
Jakarta
State/Province
DKI Jakarta
ZIP/Postal Code
15710
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Santi Gultom, MD
Phone
+6282120683216
Email
santich.gultom@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32219428
Citation
Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
Results Reference
background
PubMed Identifier
32222812
Citation
Alhazzani W, Moller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, Du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes A. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-887. doi: 10.1007/s00134-020-06022-5. Epub 2020 Mar 28.
Results Reference
background
PubMed Identifier
32217555
Citation
Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ. 2020 Mar 26;368:m1256. doi: 10.1136/bmj.m1256. No abstract available.
Results Reference
background
PubMed Identifier
15616839
Citation
Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.
Results Reference
background
PubMed Identifier
26735992
Citation
van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, Baize S, Horby PW, Raoul H, Magassouba N, Antierens A, Lomas C, Faye O, Sall AA, Fransen K, Buyze J, Ravinetto R, Tiberghien P, Claeys Y, De Crop M, Lynen L, Bah EI, Smith PG, Delamou A, De Weggheleire A, Haba N; Ebola-Tx Consortium. Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. N Engl J Med. 2016 Jan 7;374(1):33-42. doi: 10.1056/NEJMoa1511812.
Results Reference
background
PubMed Identifier
32169119
Citation
Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KS, Wang DY, Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020 Mar 13;7(1):11. doi: 10.1186/s40779-020-00240-0.
Results Reference
background
PubMed Identifier
32091533
Citation
Wu Z, McGoogan JM. 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. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
Results Reference
background
PubMed Identifier
32065057
Citation
Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, Wang YY, Xiao GF, Yan B, Shi ZL, Zhou P. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020 Feb 17;9(1):386-389. doi: 10.1080/22221751.2020.1729071. eCollection 2020.
Results Reference
background
PubMed Identifier
29984201
Citation
Rawal G, Yadav S, Kumar R. Acute Respiratory Distress Syndrome: An Update and Review. J Transl Int Med. 2018 Jun 26;6(2):74-77. doi: 10.1515/jtim-2016-0012. eCollection 2018 Jun.
Results Reference
background
PubMed Identifier
31258917
Citation
Griffiths MJD, McAuley DF, Perkins GD, Barrett N, Blackwood B, Boyle A, Chee N, Connolly B, Dark P, Finney S, Salam A, Silversides J, Tarmey N, Wise MP, Baudouin SV. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respir Res. 2019 May 24;6(1):e000420. doi: 10.1136/bmjresp-2019-000420. eCollection 2019.
Results Reference
background
PubMed Identifier
22797452
Citation
ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
Results Reference
background
PubMed Identifier
26352116
Citation
Riviello ED, Kiviri W, Twagirumugabe T, Mueller A, Banner-Goodspeed VM, Officer L, Novack V, Mutumwinka M, Talmor DS, Fowler RA. Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition. Am J Respir Crit Care Med. 2016 Jan 1;193(1):52-9. doi: 10.1164/rccm.201503-0584OC.
Results Reference
background
PubMed Identifier
32125362
Citation
Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Apr 21;323(15):1488-1494. doi: 10.1001/jama.2020.3204. Erratum In: JAMA. 2020 Apr 21;323(15):1510.
Results Reference
background
PubMed Identifier
32109013
Citation
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
Results Reference
background
PubMed Identifier
31986264
Citation
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
Results Reference
background
PubMed Identifier
32161940
Citation
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768. doi: 10.1093/cid/ciaa248.
Results Reference
background
PubMed Identifier
32085846
Citation
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available. Erratum In: Lancet Respir Med. 2020 Feb 25;:
Results Reference
background
PubMed Identifier
32213337
Citation
To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565-574. doi: 10.1016/S1473-3099(20)30196-1. Epub 2020 Mar 23.
Results Reference
background
PubMed Identifier
32219429
Citation
Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. 2020 Apr 28;323(16):1561-1562. doi: 10.1001/jama.2020.4940. No abstract available.
Results Reference
background
PubMed Identifier
25030060
Citation
Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.
Results Reference
background
Links:
URL
https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200331-sitrep-71-covid-19.pdf?sfvrsn=4360e92b_4
Description
Coronavirus disease 2019 Situation Report
URL
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.11.2000230
Description
Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020.
URL
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.11.2000266
Description
Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020
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Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome
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