Covid-19NCT04352751
Experimental Use of Convalescent Plasma for Passive Immunization in Current COVID-19 Pandemic in Pakistan in 2020
A study testing convalescent plasma in people with Covid-19, run by Hilton Pharma at 1 site in Pakistan.
Trial summary
Experimental Use of Convalescent Plasma of Passive Immunisation In Current COVID-19 Pandemic in Pakistan in 2020 Rationale \& Objective: This study would help to gather real-life setting clinical data in local population, ultimately leading to increased evidence based management of the disease condition in the said… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Covid-19
- What is being tested?
- convalescent plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 1 sitePakistan
- Study dates
- 1 May 2020to Apr 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- FOR DONORS:
- Volunteer enrolment (Informed consent will be obtained; Annexures-2A \& 2B).
- All the regulations related to ICH-GCP and Blood Transfusion Authority (BTA) Pakistan will be followed.
- Should fulfill all the criteria of a healthy blood donor (with the exception of history of COVID-19 during last 4-8 weeks.
- History of COVID-19 during last 4-8 weeks
- RT-PCR negative for SARS-CoV-2 RNA (carried out on nasopharyngeal or oropharyngeal specimen)
Show all 13Show fewer
- Age cutoff: 18-55years
- Body weight cut off: >50 kg for men and > 45kg for women
- FOR RECIPIENTS:
- Volunteer enrolment (Informed consent will be obtained; Annexures-3A \& 3B).
- Confirmed COVID-19 cases confirmed by RT-PCR laboratory tests
- Severe or Critical COVID-19 related features (8):
- Severe COVID-19, defined by the presence of any of the following features: i. Shortness of breath ii. Respiratory rate ≥ 30/min, iii. Arterial blood oxygen saturation ≤ 93%, iv. Lung infiltrates > 50% within 24 to 48 hours b. CriticalCOVID-19, defined by the presence of any of the following features: i. Respiratory failure, ii. Shock iii. Multiple organ dysfunction
Who cannot join
- Allergy history for plasma, sodium citrate and methylene blue
- For patients with history of autoimmune system diseases or selective IgA deficiency, the application of convalescent plasma should be evaluated cautiously by clinicians.
- Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multi organ failure.
Trial locations and contacts
1 site in 1 country.
Pakistan1 site, 1 recruiting
- Recruiting
National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)
Karachi, Sindh, 75300
Dr. Arshi Naz, 00923232234376, labarshi@yahoo.com
Professor Javed Akram
About this study
Experimental Use of Convalescent Plasma of Passive Immunisation In Current COVID-19 Pandemic in Pakistan in 2020 Rationale \& Objective: This study would help to gather real-life setting clinical data in local population, ultimately leading to increased evidence based management of the disease condition in the said population.
Eligibility:
Read more
- informed consent must have been obtained
- confirmed COVID-19 cases confirmed by RT-PCR laboratory tests
- moderately severe or severe life-threatening COVID-19 related features: a) Moderately Severe disease as defined by the following features: i) Shortness of breath, ii) respiratory rate ≥ 30/min, iii) arterial blood oxygen saturation ≤ 92%, iv) and/or lung infiltrates > 25% within 24 to 48 hours 67 b) Severe Life-threatening disease as defined by: i) respiratory failure, ii) shock, and/or § multiple organ dysfunction Exclusion Criteria: Allergy history of plasma, sodium citrate and methylene blue; 2. For patients with history of autoimmune system diseases or selective IgA deficiency, 3. the application of convalescent plasma should be evaluated cautiously by clinicians.
- Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multiorgan failure.
Methodology:
Total sample size is n=2000. A case report form (CRF) will have to be generated for each corona virus patient at baseline and the completion of study endpoint (at the time of discharge and at 4 weeks after experimental treatment modality using convalescent plasma.
- A unique identification number will be issued for each patient in this protocol.
- This data will be recorded in the national database. Data sources \& Analysis: Patient data originating from patient medical record and assessments (mentioned in table below) will be recorded in the study CRF. Safety data (AEs and SAEs) from any time point during the study will be recorded in the study CRF. All analyses will be performed by third party statistician on SPSS. For continuous variables, summary statistics included n (number of observations), mean, standard deviation, median, minimum and maximum values, as well as frequencies and percentages for categorical variables will be presented.
Read the detailed description
Passive immunization involves the administration of antibodies against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent. A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculums, which is likely to be much smaller than that of established disease. As an example, passive antibody therapy for pneumococcal pneumonia was most effective when administered shortly after the onset of symptoms, and there was no benefit if antibody administration was delayed past the third day of disease.
The therapeutic benefits of convalescent plasma were formally studied in animal models in early 20th century. It efficacy was first determined in 1916, when 26 poliomyelitis patients were treated with convalescent plasma from polio survivors. Subsequently, therapeutic and prophylactic significance was explored in influenza and measles. Transfusion of immune plasma is a standard treatment modality for various viral hemorrhagic fevers. Its efficacy in treating Ebola Virus Disease is also well established. Studies have reported reduction viral load in patients with H1N1 influenza. Of special attention is the meta-analysis, carried out by Mair-Jenkinset al, concluding effectiveness of passive immunization as a treatment option for severe viral acute respiratory infections caused by SARS corona virus, influenza A (H1N1), avian influenza A (H5N1) and Spanish influenza A. Efficacy of convalescent plasma has been anecdotally reported in SARS-CoV-2 infections.
- Conditions
- Covid-19
- Being tested
- convalescent plasma
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
convalescent plasmaOther
- Plasmapheresis, 900 - 1000 mL each time.
- Standard apheresis plasma collection protocol using Haemonetics MCS+ intermittent blood flow system or Terumo Optia, Cobe-Spectra, Trima or Fresenius continuous flow system to be used.
- Isovolumic saline replacement should be done.
- Each donor can donate convalescent plasma again after an interval of every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Intervention: Convalescent plasma (Frozen Solution for infusion) obtained from COVID-19 recovered patients.
The dosage depends upon the clinical situation and underlying disorder. Children: 15 ml/kg over 4-6 hours once in patients under 35 kg body weight. Adults: maximum 450 - 500 ml over 4-6 hours once in all adults patients. Receives: Other: convalescent plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in COVID-19 severity status
Improvement in disease severity will be regarded as a shift from Critical to Severe or from Severe to Mild disease category. The various disease categories are defined as following (17):
- Mild COVID-19, defined by the absence of features given in criteria for moderate and severe disease.
- Severe COVID-19, defined by the presence of any of the following features:
- Shortness of breath ii. Respiratory rate ≥ 30/min, iii. Arterial blood oxygen saturation ≤ 93%, iiii. Lung infiltrates > 50% within 24 to 48 hours c. Critical COVID-19, defined by the presence of any of the following features: i. Respiratory failure, ii. Shock iii. Multiple organ dysfunction
Measured: Up to 09 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2020
- Study start1 May 2020
- Primary completionApr 2021 (estimated)
- Study completionApr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Covid-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label, clinical trial employing WHO recognized monitored emergency use of unregistered and experimental interventions (MEURI) study.
- Masking
- None (open label)
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hilton Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Tahir Shamsi, FRCP MRCPath, Principal investigator, National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04352751
- Sponsor's protocol ID
- PIPK- 0000 /NIBD-0000/2020
- Status last verified
- Apr 2020
- First submitted
- 16 Apr 2020
- Last updated
- 29 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Robbins JB, Schneerson R, Szu SC. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis. 1995 Jun;171(6):1387-98. doi: 10.1093/infdis/171.6.1387.
PubMed 7769272Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.
PubMed 7985997Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
PubMed 21248066Luke TC, Casadevall A, Watowich SJ, Hoffman SL, Beigel JH, Burgess TH. Hark back: passive immunotherapy for influenza and other serious infections. Crit Care Med. 2010 Apr;38(4 Suppl):e66-73. doi: 10.1097/CCM.0b013e3181d44c1e.
PubMed 20154602Khan TNS, Mukry SN, Masood S, Meraj L, Devrajani BR, Akram J, Fatima N, Maqsood S, Mahesar A, Siddiqui R, Ishaque S, Afzal MB, Mukhtar S, Ahmed S, Naz A, Shamsi TS. Usefulness of convalescent plasma transfusion for the treatment of severely ill COVID-19 patients in Pakistan. BMC Infect Dis. 2021 Sep 27;21(1):1014. doi: 10.1186/s12879-021-06451-7.
PubMed 34579646
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Use of Convalescent Plasma for Passive Immunization in Current COVID-19 Pandemic in Pakistan in 2020
- ClinicalTrials.gov ID
- NCT04352751
- Acronym / sponsor ID
- PIPK- 0000 /NIBD-0000/2020
- Conditions
- Covid-19
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Hilton PharmaIndustry (pharma, biotech, devices)
- Study start
- 1 May 2020 (actual)
- Primary completion
- Apr 2021 (estimated)
- Study completion
- Apr 2021 (estimated)
- First posted
- 20 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Experimental Use of Convalescent Plasma of Passive Immunisation In Current COVID-19 Pandemic in Pakistan in 2020 Rationale \& Objective: This study would help to gather real-life setting clinical data in local population, ultimately leading to increased evidence based management of the disease condition in the said population.
Eligibility:
- informed consent must have been obtained
- confirmed COVID-19 cases confirmed by RT-PCR laboratory tests
- moderately severe or severe life-threatening COVID-19 related features: a) Moderately Severe disease as defined by the following features: i) Shortness of breath, ii) respiratory rate ≥ 30/min, iii) arterial blood oxygen saturation ≤ 92%, iv) and/or lung infiltrates > 25% within 24 to 48 hours 67 b) Severe Life-threatening disease as defined by: i) respiratory failure, ii) shock, and/or § multiple organ dysfunction Exclusion Criteria: Allergy history of plasma, sodium citrate and methylene blue; 2. For patients with history of autoimmune system diseases or selective IgA deficiency, 3. the application of convalescent plasma should be evaluated cautiously by clinicians.
- Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multiorgan failure.
Methodology:
Total sample size is n=2000. A case report form (CRF) will have to be generated for each corona virus patient at baseline and the completion of study endpoint (at the time of discharge and at 4 weeks after experimental treatment modality using convalescent plasma.
- A unique identification number will be issued for each patient in this protocol.
- This data will be recorded in the national database. Data sources \& Analysis: Patient data originating from patient medical record and assessments (mentioned in table below) will be recorded in the study CRF. Safety data (AEs and SAEs) from any time point during the study will be recorded in the study CRF. All analyses will be performed by third party statistician on SPSS. For continuous variables, summary statistics included n (number of observations), mean, standard deviation, median, minimum and maximum values, as well as frequencies and percentages for categorical variables will be presented.
Detailed description
Passive immunization involves the administration of antibodies against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent. A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculums, which is likely to be much smaller than that of established disease. As an example, passive antibody therapy for pneumococcal pneumonia was most effective when administered shortly after the onset of symptoms, and there was no benefit if antibody administration was delayed past the third day of disease.
The therapeutic benefits of convalescent plasma were formally studied in animal models in early 20th century. It efficacy was first determined in 1916, when 26 poliomyelitis patients were treated with convalescent plasma from polio survivors. Subsequently, therapeutic and prophylactic significance was explored in influenza and measles. Transfusion of immune plasma is a standard treatment modality for various viral hemorrhagic fevers. Its efficacy in treating Ebola Virus Disease is also well established. Studies have reported reduction viral load in patients with H1N1 influenza. Of special attention is the meta-analysis, carried out by Mair-Jenkinset al, concluding effectiveness of passive immunization as a treatment option for severe viral acute respiratory infections caused by SARS corona virus, influenza A (H1N1), avian influenza A (H5N1) and Spanish influenza A. Efficacy of convalescent plasma has been anecdotally reported in SARS-CoV-2 infections.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label, clinical trial employing WHO recognized monitored emergency use of unregistered and experimental interventions (MEURI) study.
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Other: convalescent plasmaIntervention: Convalescent plasma (Frozen Solution for infusion) obtained from COVID-19 recovered patients. The dosage depends upon the clinical situation and underlying disorder. Children: 15 ml/kg over 4-6 hours once in patients under 35 kg body weight. Adults: maximum 450 - 500 ml over 4-6 hours once in all adults patients. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Volunteer enrolment (Informed consent will be obtained; Annexures-2A \& 2B).
- All the regulations related to ICH-GCP and Blood Transfusion Authority (BTA) Pakistan will be followed.
- Should fulfill all the criteria of a healthy blood donor (with the exception of history of COVID-19 during last 4-8 weeks.
- History of COVID-19 during last 4-8 weeks
- RT-PCR negative for SARS-CoV-2 RNA (carried out on nasopharyngeal or oropharyngeal specimen)
Key exclusion criteria (3 listed)
- Allergy history for plasma, sodium citrate and methylene blue
- For patients with history of autoimmune system diseases or selective IgA deficiency, the application of convalescent plasma should be evaluated cautiously by clinicians.
- Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multi organ failure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| convalescent plasma* Plasmapheresis, 900 - 1000 mL each time. * Standard apheresis plasma collection protocol using Haemonetics MCS+ intermittent blood flow system or Terumo Optia, Cobe-Spectra, Trima or Fresenius continuous flow system to be used. * Isovolumic saline replacement should be done. * Each donor can donate convalescent plasma again after an interval of every 2 weeks | Other | Single Arm |
Primary outcome
Change in COVID-19 severity status
Time frame: Up to 09 days
Improvement in disease severity will be regarded as a shift from Critical to Severe or from Severe to Mild disease category. The various disease categories are defined as following (17): 1. Mild COVID-19, defined by the absence of features given in criteria for moderate and severe disease. 2. Severe COVID-19, defined by the presence of any of the following features: i. Shortness of breath ii. Respiratory rate ≥ 30/min, iii. Arterial blood oxygen saturation ≤ 93%, iiii. Lung infiltrates > 50% within 24 to 48 hours c. Critical COVID-19, defined by the presence of any of the following features: i. Respiratory failure, ii. Shock iii. Multiple organ dysfunction
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2020.
- Background: PubMed 7769272Robbins JB, Schneerson R, Szu SC. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis. 1995 Jun;171(6):1387-98. doi: 10.1093/infdis/171.6.1387.
- Background: PubMed 7985997Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.
- Background: PubMed 21248066Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
- Background: PubMed 20154602Luke TC, Casadevall A, Watowich SJ, Hoffman SL, Beigel JH, Burgess TH. Hark back: passive immunotherapy for influenza and other serious infections. Crit Care Med. 2010 Apr;38(4 Suppl):e66-73. doi: 10.1097/CCM.0b013e3181d44c1e.
- Derived from this study: PubMed 34579646Khan TNS, Mukry SN, Masood S, Meraj L, Devrajani BR, Akram J, Fatima N, Maqsood S, Mahesar A, Siddiqui R, Ishaque S, Afzal MB, Mukhtar S, Ahmed S, Naz A, Shamsi TS. Usefulness of convalescent plasma transfusion for the treatment of severely ill COVID-19 patients in Pakistan. BMC Infect Dis. 2021 Sep 27;21(1):1014. doi: 10.1186/s12879-021-06451-7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Tahir Shamsi, FRCP MRCPath principal investigator
National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing convalescent plasma in people with Covid-19, run by Hilton Pharma at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr. Arshi Naz, PhD,Diplab (00923232234376, labarshi@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in COVID-19 severity status (time frame: Up to 09 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04352751, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2020.