scholarly journals Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Karin Holm ◽  
Maria N. Lundgren ◽  
Jens Kjeldsen-Kragh ◽  
Oskar Ljungquist ◽  
Blenda Böttiger ◽  
...  
Keyword(s):  
Plasma Treatment ◽  
Viral Infections ◽  
Standard Of Care ◽  
Hospitalized Patients ◽  
Care Group ◽  
Open Label ◽  
Randomized Controlled ◽  
Oxygen Treatment ◽  
Randomized Controlled Studies ◽  
To Receive

Abstract Objective Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19. Results Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups. Trial registration ClinicalTrials NCT04600440, retrospectively registered Oct 23, 2020.

scholarly journals Convalescent plasma for hospitalized patients with COVID-19 and the effect of plasma antibodies: a randomized controlled, open-label trial

2021 ◽  
Author(s):  
Philippe Bégin ◽  
Jeannie Callum ◽  
Erin Jamulae Jamula ◽  
Richard Cook ◽  
Nancy M Heddle ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Controlled Trial ◽  
Harmful Effect ◽  
Standard Of Care ◽  
Hospitalized Patients ◽  
Open Label ◽  
Serious Adverse Events ◽  
Randomized Controlled ◽  
Negative Results ◽  
Intent To Treat

The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.

scholarly journals Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

2021 ◽  
Author(s):  
Peter W Horby ◽  
Marion Mafham ◽  
Leon Peto ◽  
Mark Campbell ◽  
Guilherme Pessoa-Amorim ◽  
...  
Keyword(s):  
Usual Care ◽  
Rate Ratio ◽  
Standard Of Care ◽  
Care Group ◽  
P Value ◽  
Open Label ◽  
Proportional Effect ◽  
Randomised Controlled ◽  
To Receive ◽  
Efficacy Population

Background: REGEN-COV is a combination of 2 monoclonal antibodies (casirivimab and imdevimab) that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and safety of REGEN-COV in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus a single dose of REGEN-COV 8g (casirivimab 4g and imdevimab 4g) by intravenous infusion (REGEN-COV group). The primary outcome was 28-day mortality assessed first among patients without detectable antibodies to SARS-CoV-2 at randomisation (seronegative) and then in the overall population. Findings: Between 18 September 2020 and 22 May 2021, 9785 patients were randomly allocated to receive usual care plus REGEN-COV or usual care alone, including 3153 (32%) seronegative patients, 5272 (54%) seropositive patients and 1360 (14%) patients with unknown baseline antibody status. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to REGEN-COV and 451 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio 0.80; 95% CI 0.70-0.91; p=0.0010). In an analysis involving all randomised patients (regardless of baseline antibody status), 944 (20%) of 4839 patients allocated to REGEN-COV and 1026 (21%) of 4946 patients allocated to usual care died within 28 days (rate ratio 0.94; 95% CI 0.86-1.03; p=0.17). The proportional effect of REGEN-COV on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity = 0.001). Interpretation: In patients hospitalised with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) reduced 28-day mortality among patients who were seronegative at baseline.

scholarly journals Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial

2021 ◽  
Author(s):  
Philippe Bégin ◽  
Jeannie Callum ◽  
Erin Jamula ◽  
Richard Cook ◽  
Nancy M. Heddle ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Harmful Effect ◽  
Standard Of Care ◽  
Hospitalized Patients ◽  
Open Label ◽  
Serious Adverse Events ◽  
Randomized Controlled ◽  
Negative Results

AbstractThe efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

scholarly journals Effectiveness and Safety of Niclosamaide as Add-on Therapy to the Standard of Care Measures in COVID-19 Management: Randomized controlled clinical trial

2021 ◽  
Author(s):  
Ahmed S. Abdulamir ◽  
Faiq I. Gorial ◽  
Sattar J Saaedi ◽  
Mohammed Fauzi Maulood ◽  
Hashim Ali Hashim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Survival Rate ◽  
Viral Infections ◽  
Standard Of Care ◽  
Antiviral Effect ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Randomized Controlled ◽  
Experimental Group

Background: COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. Methods: Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Each group was composed of 25 mild, 25 moderate and 25 severe patients. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. Results: NCS did not enhance survival rate as three of severe COVID-19 patients in NCS and in control groups died (P>0.05). However, NCS, compared to control group, reduced the time to recovery in moderate and severe COVID-19 patients about 5 and 3 days, respectively but not in mild patients (P≤0.05). Most interestingly, NCS lowered time to recovery up to five days in patients with co-morbidities (P≤0.05) whereas only one day lowered in patients without co-morbidities (P>0.05). Conclusion: It is concluded that NCS accelerates time to recovery about 3 to 5 days in moderate to severe COVID-19 patients especially those with co-morbidities; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

scholarly journals Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

2021 ◽  
Author(s):  
Peter W Horby ◽  
Guilherme Pessoa-Amorim ◽  
Natalie Staplin ◽  
Jonathan R Emberson ◽  
Enti Spata ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Usual Care ◽  
Rate Ratio ◽  
Invasive Mechanical Ventilation ◽  
Standard Of Care ◽  
Open Label ◽  
Absolute Increase ◽  
Significant Difference ◽  
Randomised Controlled ◽  
To Receive

Background: Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus 150mg aspirin once daily until discharge using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0.96; 95% confidence interval [CI] 0.89-1.04; p=0.35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1.06; 95% CI 1.02-1.10; p=0.0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0.96; 95% CI 0.90-1.03; p=0.23). Aspirin use was associated with an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in clinically significant bleeding of 0.6% (SE 0.2%). Interpretation: In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death but was associated with a small increase in the rate of being discharged alive.

scholarly journals Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Craig D. Seaman ◽  
Enrico Novelli ◽  
Laura De Castro ◽  
Margaret V. Ragni
Keyword(s):  
Unfractionated Heparin ◽  
Large Scale ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Phase Iii ◽  
Therapeutic Modality ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Open Label ◽  
Randomized Controlled

Abstract Background Acute chest syndrome (ACS) is the leading cause of mortality in sickle cell disease (SCD). The pathogenesis of ACS is complex and not entirely understood with multiple etiologies likely contributing simultaneously. One particular etiology is pulmonary vascular occlusion due to thrombosis. Thus, anticoagulation is an attractive therapeutic modality. Methods This was a single-center, randomized controlled, open-label, pilot study to determine the feasibility of performing a larger multicenter phase III trial to assess the effects of unfractionated heparin (UFH) in ACS. Subjects were randomized within 24 h of diagnosis of ACS to one of two treatment arms, UFH, and standard of care (SOC), or no UFH and SOC. UFH was given intravenously for 7 days, or until discharge, if discharge was shorter than 7 days. SOC consisted of intravenous fluids, antibiotics, supplemental oxygen, analgesia, red blood cell transfusion, and exchange transfusion. Results From July 2014 to June 2018, a total of 7 patients underwent randomization (four patients received UFH in addition to SOC and 3 patients received SOC only). Two of the prespecified feasibility criteria were not met: the capacity to consent eligible individuals and the timely notification of hospitalized patients with ACS necessary to permit randomization within 24 h of diagnosis; thus, as a result of poor enrollment, the study was terminated early. The duration of hospitalization was 279.43 (SD 267.98) and 127.31 (SD 137.70) h in the UFH and SOC arms, respectively. The duration of hypoxemia, leukocytosis, fever, and moderate to severe pain was 117.52 (SD 60.52), 24.90 (SD 29.69), 117.52 (SD 60.52), and 117.52 (SD 60.52) h, respectively, in the UFH group, and 51.49 (SD 44.79), 0, 53.11 (SD 25.06), and 88.68 (SD 72.77) h, respectively, in the SOC group. No major bleeding was noted in either group. Conclusions Our study did not achieve prespecified feasibility criteria, resulting in poor enrollment and early termination, and serves to highlight some of the pitfalls experienced in clinical research in SCD. It did show the use of UFH without any major adverse events in 7 subjects. No future large-scale study is planned. Trials registration Registered at ClinicalTrials.gov (NCT #02098993) on March 28, 2014.

Effect of Chlorhexidine Cleansing of Umbilical Cord for Prevention of Infection

2018 ◽  
Vol 4 (2) ◽  
pp. 35-39
Author(s):  
Md Khairuzzaman ◽  
MA Mannan ◽  
Abdul Matin ◽  
Mst Monjuman Ara Sarker ◽  
Nihar Ranjan Sarker ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Controlled Trial ◽  
Care Group ◽  
Cord Care ◽  
Randomized Controlled ◽  
Group 3 ◽  
Group 2 ◽  
To Receive ◽  
Level Hospital ◽  
Group 1

Background: Chlorhexidine cleansing of the cord can reduce neonatal mortality among newborns.Objective: The aim of study was to determine the effect of cord cleansing with chlorhexidine in reduction of umbilical infection among newborns in hospital settings.Methodology: This randomized controlled trial was carried out between April 2013 to July 2014 and 510 newborns were randomly assigned within a tertiary level hospital in Bangladesh to receive 1 of 3 cord care regimens single cord cleansing with 4% chlorhexidine(Group-1), multiple cord cleansing with 4% chlorhexidine (Group-2)  and clean and dry cord care (Group-3 : control).Results: The risk of umbilical cord infection (omphalitis) was significantly reduced in both the single (Relative risk [RR] 0.15 [95% CI] 0.008-0.93) and multiple chlorhexidine cleansing group (RR 0.37 [95% CI] 0.04- 0.99) compared to the dry cord care group.  The risk of omphalitis was not significantly different between multiple and single chlorhexidine cleansing group (RR 3.14 [0.13-76.54]). Conclusion: Chlorhexidine significantly reduce the risk of umbilical infection in both single and multiple cord cleansing neonates.Bangladesh Journal of Infectious Diseases 2017;4(2):35-39

scholarly journals Early treatment with inhaled GM-CSF improves oxygenation and anti-viral immunity in COVID-19 induced lung injury – a randomized clinical trial

2021 ◽  
Author(s):  
Bart Lambrecht ◽  
Karel Van Damme ◽  
Elisabeth De Leeuw ◽  
Jozefien Declercq ◽  
Bastiaan Maes ◽  
...  
Keyword(s):  
Group Treatment ◽  
Standard Of Care ◽  
Care Group ◽  
Control Group ◽  
Viral Immunity ◽  
Open Label ◽  
Hypoxemic Respiratory Failure ◽  
Gm Csf ◽  
Macrophage Colony ◽  
And Control

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) instructs monocytes to differentiate into alveolar macrophages (AM) that preserve lung homeostasis. By comparing AM development in mouse and human, we discovered that COVID-19 patients showed marked defects in GM-CSF-dependent AM instruction. The multi-center, open-label, randomized, controlled SARPAC-trial evaluated the efficacy and safety of 5 days of inhalation of rhu-GM-CSF (sargramostim, Leukine®) in 81 non-ventilated patients with COVID-19 and hypoxemic respiratory failure identified by PaO2/FiO2 ratio < 350mmHg. At day 6, more patients in the sargramostim group experienced at least 25% improvement in oxygenation compared with the standard of care group. Higher numbers of circulating class-switched B cells and effector virus-specific CD8 lymphocytes were found in the sargramostim group. Treatment adverse events, including signs of cytokine storm, were not different between active and control group. This proof-of-concept study demonstrates the feasibility and safety of inhaled GM-CSF in restoring alveolar gas exchange, while simultaneously boosting anti-COVID-19 immunity. ClinicalTrials.gov (NCT04326920).

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