scholarly journals Prevention of severe COVID-19 in the elderly by early high-titer plasma

2020 ◽  
Author(s):  
Romina Libster ◽  
Gonzalo Pérez Marc ◽  
Diego Wappner ◽  
Silvina Coviello ◽  
Alejandra Bianchi ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Primary Endpoint ◽  
High Titer ◽  
Controlled Trial ◽  
The Elderly ◽  
Elderly Subjects ◽  
Number Needed To Treat ◽  
Double Blind ◽  
Access To Treatment ◽  
Link Type

AbstractBackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression.MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible.Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%.A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed.ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives.Funded by The Bill & Melinda Gates Foundation and The Fundación INFANT Pandemic Fund. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163).All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

scholarly journals Sarilumab treatment of hospitalised patients with severe or critical COVID-19: a multinational, randomised, adaptive, phase 3, double-blind, placebo-controlled trial

2021 ◽  
Author(s):  
Francois-Xavier Lescure ◽  
Hitoshi Honda ◽  
Robert A. Fowler ◽  
Jennifer Sloane Lazar ◽  
Genming Shi ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Face Mask ◽  
Supplemental Oxygen ◽  
Rank Test ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Link Type ◽  
Hospitalised Patients ◽  
Interleukin 6 Receptor

SummaryBackgroundElevated proinflammatory cytokines have been associated with 2019 coronavirus disease (COVID-19) severity. We assessed efficacy and safety of sarilumab, an interleukin-6 receptor inhibitor, in severe (requiring supplemental oxygen by nasal canula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19.MethodsThis was a 60-day, randomised, double-blind, placebo-controlled, multinational trial in patients hospitalised with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomised 2:2:1 to intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. The primary endpoint was time to ≥2-point clinical improvement (7-point scale; range: 1 [death] to 7 [not hospitalised]). The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This trial is registered with ClinicalTrials.gov (NCT04327388).FindingsBetween March 28 and July 3, 2020, 420 patients were randomised; 416 received treatment (placebo, n=84; sarilumab 200 mg, n=159; sarilumab 400 mg, n=173). At day 29, there were no significant differences in median (95% CI) time to ≥2-point improvement between placebo (12·0 [9·0–15·0] days) and sarilumab groups (200 mg: 10·0 [9·0–12·0] days, p=0.96, log-rank test; 400 mg: 10·0 [9·0–13·0] days, p=0.34) or in proportions of patients alive (placebo, 91·7%; sarilumab 200 mg, 89·9%, p=0·63; sarilumab 400 mg, 91·9%, p=0·85). At day 29, there were numerical, nonsignificant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +9%, 95% CI −7·7 to 25·5, p=0·25) for critical patients. There were no unexpected safety signals.InterpretationThis trial did not demonstrate efficacy of sarilumab in patients hospitalised with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19.FundingSanofi and Regeneron Pharmaceuticals, Inc.

scholarly journals A randomized, double-blind, controlled trial of convalescent plasma in adults with severe COVID-19

2021 ◽  
Author(s):  
Max R. O’Donnell ◽  
Beatriz Grinsztejn ◽  
Matthew J. Cummings ◽  
Jessica Justman ◽  
Matthew R. Lamb ◽  
...  
Keyword(s):  
Normal Control ◽  
High Titer ◽  
Controlled Trial ◽  
Clinical Status ◽  
Invasive Mechanical Ventilation ◽  
Ordinal Scale ◽  
Nasopharyngeal Swab ◽  
Double Blind ◽  
Link Type ◽  
Control Plasma

AbstractBackgroundAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.ObjectiveTo evaluate the clinical efficacy and safety of convalescent plasma among adults hospitalized with severe and critical COVID-19.DesignRandomized, double-blind, controlled, multicenter, phase 2 trial conducted from April 21st to November 27th, 2020.SettingFive hospitals in New York City (NY, USA) and Rio de Janeiro (Brazil).ParticipantsHospitalized 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.InterventionParticipants were randomized 2:1 to a single transfusion of either 1 unit of convalescent or normal control plasma.MeasurementsThe primary outcome was clinical status at 28 days, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.ResultsOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to normal control plasma. At 28 days, no significant improvement in clinical status was observed in participants randomized to convalescent plasma (with an odds ratio (OR) of a 1-point improvement in the scale: 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180).However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples (n=40) from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected. Serious adverse events occurred in 39/147 (27%) participants who received convalescent plasma and 26/72 (36%) participants who received control plasma.LimitationsSome participants did not receive high-titer convalescent plasma.ConclusionIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in 28 days clinical status. The significant reduction in mortality associated with convalescent plasma, however, may warrant further evaluation.RegistrationClinicalTrials.gov, NCT04359810FundingAmazon FoundationClinical Trial RegistrationClinicalTrials.gov Identifier: NCT04359810

scholarly journals Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial

2019 ◽  
Vol 79 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Jing He ◽  
Ruijun Zhang ◽  
Miao Shao ◽  
Xiaozhen Zhao ◽  
Miao Miao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Placebo Group ◽  
Primary Endpoint ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Controlled Trial ◽  
Controlled Clinical Trial ◽  
Systemic Lupus ◽  
Double Blind ◽  
Link Type

ObjectivesOpen-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy.MethodsA randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets.ResultsAt week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells.ConclusionsLow-dose IL-2 might be effective and tolerated in treatment of SLE.Trial registration numberClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

Low Selenium Status in the Elderly Influences Thyroid Hormones

1995 ◽  
Vol 89 (6) ◽  
pp. 637-642 ◽  
Author(s):  
Oliviero Olivieri ◽  
Domenico Girelli ◽  
Margherita Azzini ◽  
Anna Maria Stanzial ◽  
Carla Russo ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Thyroid Hormones ◽  
Peroxidase Activity ◽  
Controlled Trial ◽  
The Elderly ◽  
Serum Selenium ◽  
Selenium Status ◽  
Glutathione Peroxidase Activity ◽  
Double Blind ◽  
Double Blind Placebo

1. Iodothyronine 5′-deiodinase, which is mainly responsible for peripheral triiodothyronine (T3) production, has recently been demonstrated to be a selenium-containing enzyme. In the elderly, reduced peripheral conversion of thyroxine (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid conditions of undernutrition or malnutrition, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. 3. In order to properly assess the influence of selenium status on iodothyronine 5′-deiodinase type I activity, a double-blind placebo-controlled trial was also carried out on 36 elderly subjects, resident at a privately owned nursing home. 4. In the free-living population, a progressive reduction of the T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age. A highly significant linear correlation between T4, T3/T4 and selenium was observed in the population as a whole (for T4, R = −0.312, P < 0.002; for T3/T4 ratio, R = 0.32, P < 0.01) and in older subjects (for T4, R = −0.40, P < 0.05; for T3/T4 ratio, R = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. 6. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.

scholarly journals Pelargonium sidoides root extract for the treatment of acute cough due to lower respiratory tract infection in adults: a feasibility double-blind, placebo-controlled randomised trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Merlin Willcox ◽  
Catherine Simpson ◽  
Sam Wilding ◽  
Beth Stuart ◽  
Dia Soilemezi ◽  
...  
Keyword(s):  
Primary Care ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Acute Bronchitis ◽  
Antibiotic Prescribing ◽  
Root Extract ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Link Type ◽  
Pelargonium Sidoides

Abstract Background Pelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or “Kaloba®”, is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries. Study design Feasibility double-blind randomised placebo-controlled clinical trial. Methods We aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2–4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial. Results Of 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18–21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex. Conclusions It was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition. Trial registration HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884.

scholarly journals Effects of exergame training combined with omega-3 fatty acids on the elderly brain: a randomized double-blind placebo-controlled trial

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexandra Schättin ◽  
Corinne Baier ◽  
Domenique Mai ◽  
Verena Klamroth-Marganska ◽  
Isabelle Herter-Aeberli ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Controlled Trial ◽  
The Elderly ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sander Rozemeijer ◽  
Harm-Jan de Grooth ◽  
Paul W. G. Elbers ◽  
Armand R. J. Girbes ◽  
Corstiaan A. den Uil ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Vitamin C ◽  
Organ Failure ◽  
Controlled Trial ◽  
Lung Injury Score ◽  
High Dose ◽  
Double Blind ◽  
Link Type ◽  
Search Trial ◽  
Intravenous Vitamin

Abstract Background High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. Methods This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. Discussion Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. Trial registration ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL

scholarly journals Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial

Nutrients ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 228
Author(s):  
Anxo Fernández-Ferreiro ◽  
Francisco J. Formigo-Couceiro ◽  
Roi Veiga-Gutierrez ◽  
Jose A. Maldonado-Lobón ◽  
Ana M. Hermida-Cao ◽  
...  
Keyword(s):  
Immune Response ◽  
Controlled Trial ◽  
Severe Disease ◽  
Nursing Home Residents ◽  
Vaccination Schedule ◽  
Elderly Subjects ◽  
Double Blind ◽  
Iga Antibody ◽  
Specific Igg ◽  
Antibody Levels

Elderly people are particularly vulnerable to COVID-19, with a high risk of developing severe disease and a reduced immune response to the COVID-19 vaccine. A randomized, placebo-controlled, double-blind trial to assess the effect of the consumption of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on the immune response generated by the COVID-19 vaccine in an elderly population was performed. Two hundred nursing home residents >60 yrs that had not COVID-19 were randomized to receive L. coryniformis K8 or a placebo daily for 3 months. All volunteers received a complete vaccination schedule of a mRNA vaccine, starting the intervention ten days after the first dose. Specific IgG and IgA antibody levels were analyzed 56 days after the end of the immunization process. No differences between the groups were observed in the antibody levels. During the intervention, 19 subjects had COVID-19 (11 receiving K8 vs. 8 receiving placebo, p = 0.457). Subgroup analysis in these patients showed that levels of IgG were significantly higher in those receiving K8 compared to placebo (p = 0.038). Among subjects >85 yrs that did not get COVID-19, administration of K8 tended to increase the IgA levels (p = 0.082). The administration of K8 may enhance the specific immune response against COVID-19 and may improve the COVID-19 vaccine-specific responses in elderly populations.

Efficacy and safety of HX 110-A and HX 110-B in promoting respiratory health: An 8-week, randomized, double-blind, parallel group, placebo-controlled trial

2020 ◽  
Author(s):  
Jung-Kyu Lee ◽  
Bumjo Oh ◽  
Seo-Young Yoon ◽  
Tae Yun Park ◽  
Eun Young Heo ◽  
...  
Keyword(s):  
Lung Function ◽  
Respiratory Disease ◽  
Respiratory Symptoms ◽  
Respiratory Health ◽  
Controlled Trial ◽  
Clinical Pathology ◽  
Double Blind ◽  
Parallel Group ◽  
Anti Inflammatory ◽  
Experimental Group

Abstract Background HX110-A and HX110-B are compound extracts based on radix adenophorae and rhizoma dioscoreae, respectively, which have anti-inflammatory activity. There are limited data on whether they may help improve respiratory conditions including lung function. Therefore, in this trial, we will evaluate the effectiveness and safety of the use of HX110-A and HX110-B for the treatment of respiratory health in adults with mild respiratory symptoms. Methods/design This will be an 8-week, randomized, double-blind, parallel group, placebo-controlled trial with three arms. Adults more than 40 years old with persistent respiratory symptoms will be enrolled. Patients with definite respiratory disease or with a history of recent intake of antioxidants or anti-inflammatory agents will be excluded. Study subjects will be assigned at a 1:1:1 ratio into the following three arms: controls, experimental group 1 (HX110-A), and experimental group 2 (HX110-B). Control or experimental foods will be administered for 8 weeks, and follow-up will be up to 12 weeks. The primary outcome will be total antioxidant capacity. Secondary outcomes will be inflammatory indexes, respiratory symptoms, lung function, quality of life, and fatigue level. Safety outcomes will be assessed by monitoring adverse events and vital signs, and through clinical pathology tests. Conclusion We hope that this trial will reveal the effectiveness and safety of HX110-A and/or HX110-B for medical purposes in adults with respiratory symptoms. The results should clarify if active intake of specific foods with these functional compounds may promote respiratory health in adults without definite respiratory disease.

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