meta|Evidence - COVID-19
click on circles to display study description...
convalescent plasma treatment (n=4) vs. standard of care (n=8)
randomized controlled trial low risk of bias
Convalescent plasma
Standard of care
COVID 19 all comers
Open-label.
Italy.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=11) vs. placebo (n=11)
randomized controlled trial risk of bias NA
placebo
normal saline
COVID 19 hospitalized
Double-blind.
Nigeria.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=468) vs. placebo (n=473)
randomized controlled trial some concerns about risk of bias
COVID-19 convalescent plasma (CCP)
A unit of approximately 250 mL of CCP infused within 24 hours of randomization at a rate of less than or equal to 500 mL/h.
Placebo
Equivalent volume of placebo (normal saline).
COVID 19 hospitalized
Eligible patients were adults aged 18 years or older hospitalized for 3 days or less or with symptoms of respiratory illness for 7 days or less (to include patients with presumably early phases of disease) who required noninvasive oxygen supplementation and had a positive nasopharyngeal SARS-CoV-2 reverse-transcriptase polymerase-chain-reaction test. Patients on mechanical ventilation or ECMO and patients who received a COVID-19 vaccine were excluded.
Double-blind.
21 US Hospitals at 7 centers.
WHO scale scores range from 0 to 10, with 0 indicating uninfected and no viral RNA detected and 10 indicating dead. Primary and secondary outcomes were analyzed with a bayesian proportional cumulative odds model with adjustment for the following prespecified covariates: age, sex, prerandomization WHO score, symptom duration, and the stratification variables: risk status (high vs average) and study site. CCP efficacy was defined as a cOR less than 1 and clinically meaningful effects were defined as cORs less than 0.8.
There were no prespecified stopping criteria for futility. However, after reviewing data on 920 participants on March 12, 2021, the DSMB recommended ceasing enrollment on March 15, 2021, based on slowing recruitment, the need for rapid reporting, and a 0.2% probability that the study would meet criteria for success if enrollment continued to 1000 participants.
convalescent plasma treatment (n=8) vs. placebo (n=6)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Double-blind.
United States.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=59) vs. placebo (n=15)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
Single “dose” of 2 U of convalescent plasma (total volume approximately 480 mL). Each unit of plasma (approximately 240 mL) was administered over1–4 hours, using standard hospital procedures.
Standard plasma
Single “dose” of 2 U of standard plasma (total volume approximately 480 mL). Each unit of plasma (approximately 240 mL) was administered over1–4 hours, using standard hospital procedures.
4:1 ratio.
COVID 19 hospitalized
Inclusion criteria were adult patients hospitalized with a confirmed diagnosis of COVID-19 infection from SARS-CoV-2 RT-PCR testing. The patient (or Legally Authorized Representative) needed to be willing and able to provide written informed consent.
Double-blind.
Single center: hospital in New York, United States.
Subjects never requiring intubation were assigned a time of 28 days and those who died by day 28 were assigned 0 ventilator-free days.
Enrollment in the trial was stopped on August 24,2020, after FDA granted EUA for CP since it seemed unlikely that patients would wish to participate in a randomized trial for an “approved therapy.”
convalescent plasma treatment (n=98) vs. placebo (n=46)
randomized controlled trial low risk of bias
Convalescent plasma
Placebo
Normal saline
COVID 19 hospitalized
Double-blind.
Denmark.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.Study stopped for high probability of futility
convalescent plasma treatment (n=63) vs. placebo (n=95)
randomized controlled trial some concerns about risk of bias
convalescent plasma
5 mL/kg
placebo
non convalescent plasma
COVID 19 hospitalized
double-blind
3 centers, Ecuador
Study stopped after the second interim analysis due to futility
convalescent plasma treatment (n=32) vs. placebo (n=11)
randomized controlled trial high risk of bias
Convalescent plasma
300 mL/day intravenously, on day one and day three
Placebo
Hartmann plus albumin
COVID 19 hospitalized
Double-blind.
1 center, Mexico
convalescent plasma treatment (n=20) vs. standard of care (n=11)
randomized controlled trial some concerns about risk of bias
COVID 19 hospitalized
Double-blind.
Mexico.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=43) vs. standard of care (n=43)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
300ml of convalescent plasma (with anti-SARSCoV-2 neutralizing antibody titers of at least 1:80) administered intravenously on the day of inclusion, plus standard of care. Patients without a clinical response and a persistently positive RT-PCR could receive a second plasma unit after five days.
Standard care
Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for COVID-19 was allowed in hospitals were this was part of the standard of care.
All patients received standard of care.
COVID 19 hospitalized
Patients >= 18, admitted to a study site for COVID-19 and had clinical COVID-19 disease proven by a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) test in the previous 96 hours.
Open-label.
14 secondary and academic hospitals in the Netherlands.
the trial was halted prematurely
convalescent plasma treatment (n=15) vs. standard of care (n=18)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Australia and New Zealand.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=12) vs. standard of care (n=13)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Peru.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=13) vs. standard of care (n=12)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Philippines.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.May 24, 2022 terminated : unable to achieve target sample size
convalescent plasma treatment (n=5795) vs. standard of care (n=5763)
randomized controlled trial some concerns about risk of bias
High titre convalescent plasma
plus usual care
Usual care
3 arms: usual care, usual care plus convalescent plasma or usual care plus REGN-COV2
COVID 19 hospitalized
clinically suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put them at significant risk if they were to participate in the trial
Open-label.
177 National Health Service in UK.
very preliminary results. Preliminary analysis based on 10,406 randomised patients with 1873 reported deaths
convalescent plasma treatment (n=9) vs. standard of care (n=8)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Brazil.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=38) vs. standard of care (n=36)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Spain.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=320) vs. standard of care (n=163)
randomized controlled trial some concerns about risk of bias
convalescent plasma
2 units of convalescent plasma (∼200–250 mL) were administered within 12 h after randomisation, with a second administration of 2 units24–36 h after the first administration
standard of care
COVID 19 hospitalized
open label
25 centers, Belgian
Phase 2
convalescent plasma treatment (n=17) vs. standard of care (n=14)
randomized controlled trial some concerns about risk of bias
Convalescent plasma (CCP)
Standard of care plus 200–250 mL of CCP administered intravenously during 30 min on three consecutive days.
Standard of care
COVID 19 hospitalized
Patients admitted to the hospital with a nasopharyngeal swab positive for SARS-CoV-2 in RT-PCR no later than 4 days prior to inclusion and a need for supplemental oxygen treatment to keep peripheral oxygen saturation >93%.
Open-label.
Skåne University Hospital in Lund and Helsingborg Hospital, Sweden.
Unplanned interim analysis.
The study was prematurely terminated after an interim analysis that was carried out due to increasing evidence that this treatment modality was ineffective (thirty-one of 100 intended patients had been included).
convalescent plasma treatment (n=41) vs. standard of care (n=39)
randomized controlled trial some concerns about risk of bias
convalescent plasma SOC
2 units of local convalescent plasma
soc
COVID 19 hospitalized
open- label
2 centers, USA
convalescent plasma treatment (n=20) vs. standard of care (n=10)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
United States.
Study not published yet. Results were extracetd from clinicaltrial sheets and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=60) vs. standard of care (n=60)
randomized controlled trial risk of bias NA
standard of care
COVID 19 hospitalized
Double-blind.
Italy.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=625) vs. standard of care (n=313)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
One or two units of apheresis plasma amounting to approximately 500 mL from one or two donors.
Standard of care
Usual medical care as per routine practices at each site.
COVID 19 hospitalized
Inclusion: 1. ≥16 years of age (≥18 years of age in the United States, Brazil, and Israel) 2. Admitted to hospital for confirmed COVID-19 respiratory illness3. Receiving supplemental oxygen4. 500 mL of ABO compatible CCP is available. Exclusion: 1. Onset of signs or symptoms of COVID-19 respiratory illness >12 days prior to randomization (eg. cough, chest pain,dyspnea, or hypoxia)2. Intubated or plan in place for intubation3. Plasma is contraindicated (e.g. history of anaphylaxis from transfusion)4. Decision in place for no active treatment.
Open-label.
72 hospital sites in Canada, US, and Brazil.
Trial was prematurely stopped at planned interim analysis for futility (see. concor1.ca web site)
convalescent plasma treatment (n=200) vs. standard of care (n=200)
randomized controlled trial some concerns about risk of bias
Convalescent Plasma
Dose-250 ml Frequency - 2 doses on consecutive days Duration
Standard of care
COVID 19 hospitalized
open-labelled
2 centers, India
convalescent plasma treatment (n=150) vs. standard of care (n=151)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=15) vs. standard of care (n=15)
randomized controlled trial some concerns about risk of bias
Recovered COVID-19 plasma
Single dose of plasma of recovered COVID-19 individuals, 250 ml, plus standard COVID-19 therapy.
Standard of care
Available standard therapy included: supplemental oxygen, noninvasive and invasive ventilation, antibiotic medication, inotrope drugs, renal-replacement therapy, anticoagulants, glucocorticoids, intravenous fluids, interferon, and extracorporeal membrane oxygenation (ECMO).
COVID 19 hospitalized
Hospitalized patients ≥18 years, with confirmed positive nasopharyngeal/oropharyngeal covid-19 swab, and have two or more of a fourcategory illness-severity scale: 1. Respiratory frequency ≥24/min. 2. Blood oxygen saturation ≤ 93% on room air, 3. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 mmHg, 4. Pulmonary infiltrates occupying more than 50% of both lungs. Any patient with prior allergic history to plasma or plasma products or septic shock or multiple organ failure was excluded from the study.
Open-label.
Single center, Qena University Hospital, Egypt.
50% Improvement of severity of illness was defined as achieving a minimum of two-point reduction on the four-category illnessseverity scale: Respiratory frequency ≥ 24/min; blood oxygen saturation ≤ 93% on room air; partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 mmHg; pulmonary infiltrates occupying more than 50% of both lungs, during 5 days study period.
convalescent plasma treatment (n=241) vs. standard of care (n=246)
randomized controlled trial some concerns about risk of bias
convalescent plasma
200 mL from 1 to a maximum of 3 infusions
SOC
COVID 19 hospitalized
open-label
27 centers, Italy
convalescent plasma treatment (n=179) vs. standard of care (n=171)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
One dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2 (ratio ≥1.1 with the Euroimmun ELISA test; Euroimmun,Lübeck, Germany)
Standard of care
Standard of care only ( including all supportive and specific treatments with off-label marketed medicines used according to local or national recommendations).
All patients in both groups received standard of care.
COVID 19 hospitalized
Patients hospitalized for laboratory-confirmed SARS-CoV-2 infection (RT-PCR) with either radiographic evidence of pulmonary infiltrates or clinical evidence plus SpO2 ≤94% on room air, and within 12 days from the onset of symptoms (fever or cough).
Open-label.
27 hospitals in Spain.
The patient’s clinical status was recorded using the seven-category ordinal COVID-19 scale: 1, not hospitalized, no limitations on activities; 2, not hospitalized, limitation on activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, on non-invasive ventilation or high flow oxygen devices; 6, hospitalized,on invasive mechanical ventilation or ECMO and 7, death.
The trial was temporarily stopped on July 10, 2020, after the first interim analysis, due to a drastic fall in recruitment (end of first wave in Spain), although prespecified futility or efficacy stop criteria had not been reached. The trial recruitment was resumed shortly after, with the surge of the second wave, and the trial was finally completed as planned.
convalescent plasma treatment (n=40) vs. standard of care (n=20)
randomized controlled trial low risk of bias
COVID 19 hospitalized
Open-label.
Bangladesh.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=67) vs. standard of care (n=69)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
Standard of care plus convalescent plasma administered over look 2-3 hours at a rate of 1.4-2mL/min and a second aliquot transfused at the same rate 3 hours after completion of the first one.
Standard of care
The SOC was according to the Uganda COVID-19 case management guidelines.
COVID 19 hospitalized
Open-label.
Single center: MNRH in Kampala, Uganda.
convalescent plasma treatment (n=80) vs. placebo (n=80)
randomized controlled trial low risk of bias
Convalescent plasma
250 ml of convalescent plasma with an IgG titer greater than 1:1000 against SARS-CoV-2 spike (S) protein (COVIDAR IgG, Instituto Leloir, Argentina).
Placebo
250 ml of placebo (0.9% normal saline).
Convalescent plasma or placebo was administered less than 72 hours after the onset of symptoms, and the infusions were given over a period of 1.5 to 2.0 hours. None of the patients received any experimental therapy for Covid-19 besides convalescent plasma.
COVID-19 mild to moderate
Patients who were 75 years of age or older, irrespective of current coexisting conditions, or between 65 and 74 years of age with at least one coexisting condition were identified and assessed for eligibility. At the time of screening for SARS-CoV-2 by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, eligible patients had had at least one of each sign or symptom in the following two categories for less than 48 hours: a temperature of at least 37.5, unexplained sweating, or chills; and dry cough, dyspnea, fatigue, myalgia, anorexia, sore throat, dysgeusia, anosmia, or rhinorrhea.
Double-blind
Clinical sites and geriatric units in Argentina
The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.
convalescent plasma treatment (n=235) vs. standard of care (n=229)
randomized controlled trial high risk of bias
Convalescent plasma
Two doses of 200 mL CP was transfused 24 hours apart plus best standard of care
Standard of care
Best standard of care only
SoC in both groups
COVID-19 mild to moderate
The trial was conducted in 39 hospitals across India, with some level of heterogeneity across the trial sites for best standard of care and participantenrolment.
Open-label.
39 public and private hospitals across India.
Phase 2.
convalescent plasma treatment (n=150) vs. placebo (n=73)
randomized controlled trial low risk of bias
Convalescent plasma
Single unit of plasma (~200-250 milliliters) transfused over approximately 2 hours.
Normal control plasma
Single unit of plasma (~200-250 milliliters) transfused over approximately 2 hours.
Convalescent plasma collected from patients who had recovered from laboratory-confirmed COVID-19 with a minimum anti-SARS-CoV-2 total IgG antibody titer of ≥1:400. Control plasma consisted of oldest available plasma at each study site without prior testing for anti-SARS-CoV-2 antibodies and collected prior to January 1st, 2020 in Rio de Janeiro and February 20th, 2020 in New York City.
COVID-19 severe or critically
Hospitalized patients aged ≥18 years with laboratory-confirmed COVID-19, infiltrates on chest imaging and oxygen saturation ≤ 94% on room air or requirement for supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation
Double-blind.
5 hospitals in New York City, USA and Rio de Janeiro, Brazil.
The primary outcome was measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population. The ordinal scale is based on that recommended by the World Health Organization : 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; 6, hospitalized, requiring ECMO, IMV, or both; 7, death.
Phase II.
convalescent plasma treatment (n=228) vs. placebo (n=106)
randomized controlled trial low risk of bias
Convalescent plasma
Single administration of Covid-19 convalescent plasma in addition to standard treatment. The convalescent plasma infused volume was defined within the range of 5-10 ml/kg with aninferior limit around 400 ml for patients whose body weight was below 70 kg and a superior limitof 600 ml for those above 70 kg.
Placebo
Single dose of normal saline solution in addition to standard treatment.
2:1 ratio. Patients were allowed to receive antiviral agents, glucocorticoids, or both according to the standard of care at the provider health care institution.
COVID-19 severe or critically
Reverse-transcriptase–polymerase-chain-reaction (RT-PCR) positive for SARS-CoV-2, radiologically confirmed pneumonia, no previous directives rejecting advanced life support, and at least one of the following severity criteria: oxygen saturation (SaO2) below 93% while they were at rest and breathing ambient air, a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) below 300 mm Hg (PaO2 :FiO2), or a Sequential Organ Failure Assessment (SOFA) or modified SOFA (mSOFA) score of two or more points above baseline status.
Double blind.
12 clinical sites in Argentina (coordinated by Hospital Italiano de Buenos Aires).
Adapted version of the World Health Organization (WHO) clinical scale: 1 indicated death, 2 invasive ventilatory support, 3 hospitalized with supplemental oxygen requirement, 4 hospitalized without supplemental oxygen requirement, 5 discharged without full return to baseline physicalfunction, and 6 discharged with full return to baseline physical function.
convalescent plasma treatment (n=14) vs. placebo (n=15)
randomized controlled trial high risk of bias
Convalescent plasma (COPLA)
500 mL of convalescent plasma from recovered COVID-19 patients, in two divided doses on consecutive days to avoid transfusion-related volume overload.
Fresh Frozen Plasma (FFP)
FFP transfused in the study was collected before the emergence of the virus in India to avoid any chance of providing COVID-19 convalescent plasma in the SMT group. Transfusion of 500 mL of FFP in two divided doses on consecutive days to avoid transfusion-related volume overload.
Standard medical care in both groups: All the patients in the study were initiated on supplemental oxygen at five litter/min with target SpO2 being ≥94%. All patients received a course of Hydroxychloroquine 400 mg BD on Day1, followed by 200 mg BD for five days along with Oral Azithromycin 500 mg OD for five days.
COVID-19 severe or critically
Severe COVID -19 infections defined as WHO interim guidance and the guideline of diagnosis and treatment of COVID-19 of national health commission of china (version 5.0)
Open-label.
1 center, Lok Nayak Hospital, New Delhi, India.
Phase II.
phase 2
convalescent plasma treatment (n=20) vs. standard of care (n=20)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
400 mL of CP, given as 200ml over 2hrs over 2 successive days; the infusion rate was monitored and amended if there was a risk of fluid overload.
Standard of care
The standard supportive treatment included control of fever (paracetamol) and possible therapy including antiviral medications, Tocilizumab and antibacterial medication.
Patients prior to CP therapy were on standard supportive treatment including control of fever (paracetamol) and possible therapy including antiviral medications, Tocilizumab and antibacterial medication.
COVID-19 severe or critically
Patients with COVID-19 diagnosis based on polymerase chain reaction (PCR) testing, hypoxia (Oxygen saturation of less than or equal 92% on air, or PO2 < 60mmHg in arterial blood gas, or arterial partial pressure of oxygen (PaO )/fraction of inspired oxygen (FIO) of 300 or less) and patient requiring oxygen therapy, pneumonia confirmed by chest imaging. Patients requiring ventilatory support (invasive or non-invasive) were excluded.
Open-label.
Two medical centres in Bahrain.
Pilot trial.
convalescent plasma treatment (n=40) vs. standard of care (n=40)
randomized controlled trial high risk of bias
Convalescent plasma
Two consecutive doses of ABO-matched 200ml convalescent plasma on two consecutive days, the first transfusion being on the day of enrolment, in addition to standard of care.
Standard of care
Most of patients received Hydroxychloroquine 400 mg BD on first day followed by 400 mg OD for four days, Azithromycin 500mg OD for 5 days, Ivermectin 12 mg OD for 5days and Doxycyclin 100 mg BD for 10 days.
Standard of care in both groups. All patients with evidence for ARDS received O2 therapy as per requirement, either intravenous or oral corticosteroids. Prophylactic or therapeutic anticoagulation, appropriate broad-spectrum antibiotic, antidiabetic therapy and anti-hypertensive agents if needed.
COVID-19 severe or critically
COVID-19 patients with severe disease (fever or suspected respiratory infection, plus one of the following; respiratory rate >30 breaths/min, severe respiratory distress, SpO2< 90% at room air) with mild ARDS, defined as patients having partial pressure of oxygen in the arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio of 200-300 mmHg or moderate ARDS, defined as PaO2/FiO2 100-200 mmHg, not on mechanical ventilation.
Open-label.
Single center,
Phase II. No plan statistical available.
convalescent plasma treatment (n=21) vs. standard of care (n=28)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
400 mL of frozen convalescent plasma transfused over 2 hours, The convalescent plasma was given only once for all of the patients in the CP group.
Standard of care
Included patients, whether in CP or control group, were exactly on the same protocol of therapy: hydroxychloquine 200 mg twice per day for at least 10 days plus azithromycin once 500 mg/day loading dose, followed by 250mg once per day for 5 days plus oxygen therapy plus methylprednisolone 40 mg per day after admissionto RCU.
COVID-19 severe or critically
Adult patients ≥18, with SpO2 <90% in resting state, affected by pneumonia at their first 3 days in RCU receiving O2 or on ventilators.
Open-label.
Multicenter, 3 hospitals in Baghdad, Iraq.
Recovery or death, length of stay inhospital, and improvement in the clinical course ofthe disease were monitored clinically.
convalescent plasma treatment (n=49) vs. standard of care (n=51)
randomized controlled trial some concerns about risk of bias
convalescent plasma hydroxychloroquine azithromycine
500 milliliters of convalescent plasma, distributed in two 250 milliliters transfusions on the first and second day. azithromycin (500 milligrams daily) and hydroxychloroquine (400 milligrams each 12 hours) for 10 days
hydroxychloroquine azithromycin
hydroxychloroquine 400 milligrams each 12 hours for 10 days ; azithromycin 500 milligrams daily for 10 days
COVID-19 severe or critically
open-label, randomized
3 centers, colombia
multiple testing estimated enrollment : 80 participants
convalescent plasma treatment (n=1095) vs. standard of care (n=916)
randomized controlled trial low risk of bias
Convalescent plasma
High-titer ABO compatible convalescent plasma (total volume approximately 550 /- 150 ml) within 48 hours of randomization
Standard of care
COVID-19 severe or critically
REMAP-CAP exclusion criteria included presumption that death was imminent with lack of commitment to full support, or participation in REMAP-CAP in the prior 90 days.
Open-label.
129 sites in UK, Australia, US, Canada.
In this composite ordinal outcome, all deaths within the hospital, up to day 90, are assigned the worst outcome (–1 day). Among survivors, respiratory and cardiovascular organ support-free days were calculated up to day 21, such that a higher number represents faster recovery.
The convalescent plasma intervention was stopped after pre-specified criteria for futility were met.
convalescent plasma treatment (n=31) vs. standard of care (n=31)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
One unit (500 mL) plasma on the admission day plus standard drugs. The first plasma unit was injected in the first 4 h after admission; according to the physician’s recommendation, the second unit was prescribed if no improvement was observed after 24 h.
Standard of care
Five patients required the administration of the second unit of plasma. All patients received similar antiviral therapy, including Ritonavir/Lopinavir, and chloroquine phosphate.
COVID-19 severe or critically
1- COVID-19 patients who had specifed COVID-19 symptoms (less than 7 days since the onset of the symptoms).2- The positive results of PCR test and CT scan.3- Severity WHO score>4.4- Blood oxygen saturation (SPO2) ≤93% in room air. 5- Individuals who no exhibit hypersensitivity to plasma intravenous administration.6- Those who voluntarily signed the informed consent.
Single-blind.
Single center: emergency departement in Razi hospital of Ahvaz, Iran.
In the register, primary endpoints were: Complete remission of clinical signs, negative qRT-PCR test, and improved CT scan. (7-14 days after starting the treatment).
convalescent plasma treatment (n=53) vs. standard of care (n=52)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
3 units of CCP: The administration of CCP should commence within 1 day after randomization, one transfusion unit each of CCP was given on day 1, 3 and 5.
Standard of care
Standard treatment alone.
Seven patients randomized to the control group crossed over to receive CCP after assessment on day 14 because of progressive COVID-19 (failure of primary outcome). Patients in the crossover group also received one unit of CCP on three days. Patients in both groups received other anti-viral treatment and/or supportive treatment according to institutional standard procedures.
COVID-19 severe or critically
(1) SARS CoV-2 infection confirmed by PCR (bronchoalveolar lavage, sputum, nasal and/or pharyngeal swap); (2) age ≥ 18 years and ≤ 75 years and (3) severe disease defined by at least one of the following: a)respiratory rate ≥ 30 breaths / minute under ambient air; b) requirement of any type of ventilation support (defined as supplemental oxygen or non-invasive ventilation or invasive ventilation or ECMO); c) needs treatment on ICU; (4) written informed consent by patient or representative.
Open-label.
Multicenter, 13 hospitals in Germany.
convalescent plasma treatment (n=43) vs. standard of care (n=47)
randomized controlled trial low risk of bias
A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition.
COVID-19 severe or critically
Open-label.
Germany.
Study not published yet. Results and risk of bias assessment were extracted from Axfors C. et al meta-analysis https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06829-7?s=09.
convalescent plasma treatment (n=80) vs. standard of care (n=80)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
Two infusions 48 hours apart of 300ml of CP plus Standard of Care (SOC).
Standard of care
Standard of care alone.
All patients in both groups received standard of care. The SOC for COVID-19 was at the discretion of the treating physicians. The use of glucocorticoids, other immunomodulators, antibiotic agents, and antiviral agents was allowed. Remdesivir was not available in Brazil during the trial period.
COVID-19 severe or critically
18 or older, positive reverse transcriptase polymerase chain reaction (RT-PCR) for SARSCoV-2, less than 15 days of initial symptoms onset, and severe respiratory disease, as defined by the presence of at least one of the following: respiratory rate >30 breaths per minute in room air; oxygen saturation (O2) ≤93% in room air; arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 300; need for supplemental O2 to maintain O2 saturation >95%; need for supplemental O2 by high flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation.
Open-label.
Single center: single COVID-19 reference hospital, Porto Alegre, Brazil.
Clinical improvement was defined as hospital discharge or reduction of 2 points in a 6-level ordinal scale defined as follows; 1, not hospitalized; 2, hospitalized and not receiving supplemental oxygen; 3, hospitalized and receiving supplemental oxygen; 4, hospitalized and receiving oxygen supplementation administered by a high-flow nasal cannula or noninvasive ventilation; 5, hospitalized and receiving mechanical ventilation or extracorporeal membrane oxygenation; and 6, death.
One pre-planned interim analysis for efficacy and safety evaluation after 80 patients with complete follow-up was conducted. The stopping rule for efficacy and safety was a P value<.05. There was no adjustment in the final threshold for statistical significance for sequential analysis.
convalescent plasma treatment (n=52) vs. standard of care (n=51)
randomized controlled trial some concerns about risk of bias
Convalescent plasma
Thetransfusion dose of COVID-19 convalescent plasma was approximately 4 to 13 mL/kg of recipient bodyweight. Convalescent plasma transfusion was administered at approximately 10mLfor the first 15 minutes, which was then increased to approximately 100 mL per hour with close monitoring.
standard treatment alone.
Standard treatment consisted of symptomatic control and supportive care for COVID-19, mostly based on the evolving Chinese national COVID-19 treatment guidelines and hospital practice. Possible treatments included antiviral medications, antibacterial medications, steroids, human immunoglobulin, Chinese herbal medicines, and other medications.
SoC in both groups.
COVID-19 severe or critically
Open-label
7 medical centers in Wuhan, China,
Clinical improvement defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]).
powered by vis.js Network