Safety and immunogenicity of inactivated SARS-CoV-2 vaccine in high-risk occupational population: a randomized, parallel, controlled clinical trial

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population. Methods In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis. Results A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0–14, 0–21, and 0–28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95% CI: 88.4–108.4) in the 0–14 group, which was significantly lower compared with 134.4 (95% CI: 123.1–145.7) in the 0–21 group (P < 0.001 vs 0–14 group) and 145.5 (95% CI: 131.3–159.6) in the 0–28 group (P < 0.001 vs 0–14 group), resulting in the seroconversion rates to neutralizing antibodies (GMT ≥ 16) of 100.0% for all three groups, respectively. The intention-to-treat (ITT) analysis yielded similar results. All reported adverse reactions were mild. Conclusions Both a two-dose of inactivated SARS-CoV-2 vaccine at 0–21 days and 0–28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0–14 days regimen in high-risk occupational population, with seroconversion rates of 100.0%. Trial registration Chinese Clinical Trial Registry, ChiCTR2100041705, ChiCTR2100041706. Registered 1 January 2021, www.chictr.org.cn. Graphical Abstract

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Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccine in High-Risk Occupational Population: a randomized, parallel, controlled clinical trial

10.1101/2021.08.06.21261696 ◽

2021 ◽

Author(s):

Yongliang Feng ◽

Jing Chen ◽

Tian Yao ◽

Yue Chang ◽

Xiaoqing Li ◽

...

Keyword(s):

Clinical Trial ◽

High Risk ◽

Adverse Reactions ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Controlled Clinical Trial ◽

Trial Registry ◽

Clinical Trial Registry ◽

Global Spread ◽

To Receive

Vaccination is urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we conducted a randomized, parallel, controlled clinical trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval for high-risk occupational population. Participants were randomly assigned to receive two doses of inactivated SARS-CoV-2 vaccine at an interval of either 14 days, 21 days or 28 days. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Our results showed that the seroconversion rates (GMT ≥ 16) were all 100% in the three groups and the 0-21 and 0-28 groups elicited significantly higher SARS-CoV-2 neutralizing antibody level. All reported adverse reactions were mild. (Chinese Clinical Trial Registry: ChiCTR2100041705, ChiCTR2100041706)

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Neutralizing Antibody Therapeutics for COVID-19

Viruses ◽

10.3390/v13040628 ◽

2021 ◽

Vol 13 (4) ◽

pp. 628

Author(s):

Aeron C. Hurt ◽

Adam K. Wheatley

Keyword(s):

High Risk ◽

Neutralizing Antibodies ◽

Controlled Trial ◽

Antiviral Treatment ◽

Severe Disease ◽

Neutralizing Antibody ◽

Supplemental Oxygen ◽

European Medicines Agency ◽

Global Public Health ◽

Public Health Burden

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant “escape” mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.

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Efficacy and safety of berberine for dyslipidemia: study protocol for a randomized double-blind placebo-controlled trial

Trials ◽

10.1186/s13063-021-05028-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ying Zhao ◽

Yuan-Yuan Yang ◽

Bao-Lin Yang ◽

Ya-Wei Du ◽

Da-Wei Ren ◽

...

Keyword(s):

Clinical Trial ◽

Controlled Trial ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Controlled Clinical Trial ◽

Atherosclerotic Cardiovascular Disease ◽

Efficacy And Safety ◽

Clinical Trial Registry ◽

High Quality ◽

Double Blind

Abstract Background Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a leading cause of death worldwide. The clinical utility of commonly used lipid-lowering drugs such as statins and fibrates is sometimes limited by the occurrence of various adverse reactions. Recently, berberine (BBR) has received increasing attention as a safer and more cost-effective option to manage dyslipidemia. Thus, a high-quality randomized controlled trial to evaluate the efficacy and safety of BBR in the treatment of dyslipidemia is deemed necessary. Methods/design This is a randomized, double-blind, and placebo-controlled clinical trial. A total of 118 patients with dyslipidemia will be enrolled in this study and randomized into two groups at a ratio of 1:1. BBR or placebo will be taken orally for 12 weeks. The primary outcome is the percentage of low-density lipoprotein cholesterol reduction at week 12. Other outcome measures include changes in other lipid profiles, high sensitivity C-reactive protein, blood pressure, body weight, Bristol Stool Chart, traditional Chinese medicine symptom form, adipokine profiles, and metagenomics of intestinal microbiota. Safety assessment includes general physical examination, blood and urine routine test, liver and kidney function test, and adverse events. Discussion This trial may provide high-quality evidence on the efficacy and safety of BBR for dyslipidemia. Importantly, the findings of this trial will help to identify patient and disease characteristics that may predict favorable outcomes of treatment with BBR and optimize its indication for clinical use. Trial registration Chinese Clinical Trial Registry ChiCTR1900021361. Registered on 17 February 2019.

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Xuesaitong Capsule For Patients After Percutaneous Coronary Intervention For Unstable Angina: Study Protocol For a Randomized Controlled Trial

10.21203/rs.3.rs-673264/v1 ◽

2021 ◽

Author(s):

Yanqiao Yu ◽

Shengyao Li ◽

Wenhui Duan ◽

Jinwen Luo ◽

Yihan Zhao ◽

...

Keyword(s):

Clinical Trial ◽

Percutaneous Coronary Intervention ◽

Unstable Angina ◽

Conventional Treatment ◽

Controlled Trial ◽

Blood Lipid ◽

Coronary Intervention ◽

Controlled Clinical Trial ◽

Clinical Trial Registry ◽

Percutaneous Coronary

Abstract • Background: This study was designed to investigate the effect of Xuesaitong (XST) capsule added to conventional treatment in patients after percutaneous coronary intervention (PCI) for unstable angina (UA).• Methods: This is a 12-week, randomized, multi-center, double-blinded, placebo-controlled clinical trial. A total of 120 patients with UA will be recruited and randomly allocated in a 1:1 ratio to receive XST or placebo (2 capsules twice per day) on the background of conventional treatment. The changed level of high-sensitivity C-reactive protein from baseline to week 12 is the primary outcome. Secondary outcomes include tumor necrosis factor-α, interleukin-6, platelet aggregation, blood lipid, angina symptoms and ST segment deviation in electrocardiogram. The safety of XST will be monitored during the trial.• Discussion: This study will provide an evidence regarding the efficacy and safety of XST on the background of conventional medical treatment in patients after PCI for UA.• Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032152. Registered on 14 January 2020.

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The effect of Xuanbai Chengqi decoction on patients with pneumonia-derived sepsis: study protocol for a randomized controlled trial

10.21203/rs.2.16361/v2 ◽

2020 ◽

Author(s):

Zhang Jun ◽

Yi Yu ◽

Bojun Zheng ◽

Huang Jing

Keyword(s):

Clinical Trial ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Controlled Trial ◽

Antibiotic Use ◽

Lavage Fluid ◽

Plateau Pressure ◽

Lung Compliance ◽

Controlled Clinical Trial ◽

Clinical Trial Registry

Abstract Background: Sepsis and septic shock are major healthcare problems. pneumonia-derived is one of the important aspects of sepsis. The theory of traditional Chinese medicine (TCM) dictates that diseases of the lung and those of the large intestine react with each other. Methods/Design: A single-blind, randomised controlled clinical trial will be conducted involving 90 patients with pneumonia-derived sepsis. Participants will be randomised at a 1:1 ratio to receive Xuanbai Chengqi decoction (XCD) (experimental arm) or the same amount of saline treatment (control arm). The intervention will comprise one session/day for 1 week. The primary outcomes will be 28-day mortality, and levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid and serum and static lung compliance, dynamic lung compliance, plateau pressure, and peak airway pressure, 1, 3 and 7 days after treatment completion with respect to baseline levels. Secondary outcomes will be the symptom score of traditional Chinese medicine, duration of parenteral nutrition, prevalence of complications and the course of antibiotic use. Measurements will be taken at baseline, 1, 3 and 7 days during the intervention, after 28 days after completing the intervention. Adverse events between arms will be evaluated. Discussion: This is the first trial to evaluate the effects of XCD on management of pneumonia-derived sepsis. If the results are as expected, they will provide evidence of XCD in promoting the results in pneumonia-derived sepsis patients. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900024072. Registered on 24 June 2019.

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Therapeutic Evaluation of Artesunate in IgA Nephropathy (TEATING) Study: A study protocol of a multicenter, double-blind, randomized, placebo-controlled trial

10.21203/rs.3.rs-324565/v1 ◽

2021 ◽

Author(s):

Qi Chen ◽

Zi Wang ◽

Jicheng Lv ◽

Lijun Liu ◽

Hang Li ◽

...

Keyword(s):

Clinical Trial ◽

Iga Nephropathy ◽

Clinical Evidence ◽

Kidney Diseases ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

Clinical Trial Registry ◽

Double Blind ◽

Patients At Risk ◽

Stage Renal Disease

Abstract Background IgA nephropathy is the most common glomerular disease and a common cause of progression to end-stage renal disease in patients with kidney diseases. Proteinuria levels are critical to the prognosis of patients with IgA nephropathy, but many patients are still unable to effectively control proteinuria levels after receiving adequate RAAS blockers. Antimalarial drugs have shown good efficacy in the treatment of kidney disease in previous studies; however, there have been no strict designed randomized controlled trials to confirm the clinical efficacy of artesunate in IgA nephropathy patients. Therefore, we designed this clinical trial to compare the effect of artesunate versus placebo in patients with IgA nephropathy. Methods This study was a randomized, double-blind, three-group-parallel, placebo-controlled clinical trial. One hundred and twenty eligible IgA nephropathy patients at risk of progression were randomly divided into artesunate 100mg group, artesunate 50 mg group, and placebo group. Changes in proteinuria and renal function were measured after 6 months of intervention. The levels of Gd-IgA1, Anti-Gd-IgA1 in the patient's blood will also be tested to further understand possible immune mechanisms. Discussion Clinical evidence for artesunate treatment of IgA nephropathy is currently lacking, and we expect that the results of this trial will provide high-quality clinical evidence for artesunate as a treatment option for IgA nephropathy in the future. Trial registration: Chinese Clinical Trial Registry: ChiCTR2000038104, registration date: 10 September 2020. http://www.chictr.org.cn/edit.aspx?pid=61338&htm=4.

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High dose vitamin C in sepsis (HDVCIS): study protocol for a randomized controlled trial

10.21203/rs.3.rs-703922/v1 ◽

2021 ◽

Author(s):

Bing Zhao ◽

Mengjiao Li ◽

Jian Li ◽

Leshan Liu ◽

Yihui Wang ◽

...

Keyword(s):

Clinical Trial ◽

Vitamin C ◽

Animal Studies ◽

Controlled Trial ◽

Small Scale ◽

Controlled Clinical Trial ◽

High Dose ◽

Clinical Trial Registry ◽

Double Blind ◽

High Dose Vitamin

Abstract Sepsis is an inflammatory syndrome with life-threatening organ dysfunction resulting from a dysregulated host response to infection. Although the treatment for sepsis has improved a lot in the last 30 years, sepsis related mortality remains high. In the recent 10 years, high dose intravenous injection of vitamin C, the first line antioxidant of human, has received more and more attention in the field of critical care, its beneficial effect has been demonstrated by several small scale clinical trial and animal studies, but the effect of high dose vitamin C on sepsis in a larger trial seems warranted in further study. Here we will conduct a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial named as HDVCIS. The trial protocol has been approved by Clinical Trail Ethics Committee of Ruijin Hospital of Shanghai JiaoTong University School of Medicine. This trial has been registered in Chinese Clinical Trial Registry (ChiCTR1800017633) in August 7, 2018. Patients will be recruited from 4 medical centers in China. Its object is to testify the efficacy and safety of high dose vitamin C in the treatment of sepsis.

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Baidu Jieduan Granule in the Treatment of Coronavirus Disease-2019 (COVID-19): Study Protocol for an Open-Label Randomized Controlled Clinical Trial

10.21203/rs.3.rs-44542/v1 ◽

2020 ◽

Author(s):

Wen Zhang ◽

Qin Xie ◽

Xiaoming Xu ◽

Shuting Sun ◽

Tian Fan ◽

...

Keyword(s):

Clinical Trial ◽

Controlled Trial ◽

Theory And Practice ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Clinical Trial Registry ◽

Open Label ◽

Randomized Controlled ◽

Epidemic Diseases

Abstract Background: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive impact on human health. Due to the absence of antiviral medicine for COVID-19 thus far, it is desperately need to develop the effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, hoping to produce clinical efficacy and decrease the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Baidu Jieduan Granule in curing COVID-19. Methods/design: This multicenter, open-label randomized controlled trial is conducted 300 cases with COVID-19. The patients will be randomly (1:1) divided into treatment group or control group. All cases will receive standard therapy at the same time. The experiment group will receive Baidu Jieduan Granule treatment twice a day for 14 days. The outcomes are assessed at baseline and at 3, 5, 7, 14 days after treatment initiation. The primary outcome is the rate of symptom (fever, fatigue, and coughing) recovery. Adverse events will be monitored throughout the trial.Discussion: The study will provide a high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan Granule in treatment of severe COVID-19, and also enrich the theory and practice of TCM in treating COVID-19. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029869. Registered on 15 February 2020

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Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies

Transfusion Medicine and Hemotherapy ◽

10.1159/000515610 ◽

2021 ◽

pp. 1-10

Author(s):

Sixten Körper ◽

Bernd Jahrsdörfer ◽

Victor M. Corman ◽

Jan Pilch ◽

Patrick Wuchter ◽

...

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Controlled Clinical Trial ◽

Neutralizing Capacity ◽

Iga Antibodies ◽

Antibody Titers ◽

Antibody Levels ◽

Over Time

Background: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. Methods: Patients who had recovered from COVID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. Results: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. Conclusion: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

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Traditional Chinese Medicine (Xiao Tan San Jie Granule) for Covid-19 Patients in Rehabilitation Stage: Study Protocol for a Randomized Controlled Trial

10.21203/rs.3.rs-80068/v1 ◽

2021 ◽

Author(s):

Yingshuai Li ◽

Junwen Han ◽

ying Zhang ◽

Ji Wang ◽

Jiangming He ◽

...

Keyword(s):

Clinical Trial ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Outcome Assessment ◽

Virus Disease ◽

Controlled Trial ◽

Secondary Outcome ◽

Controlled Clinical Trial ◽

Clinical Trial Registry ◽

Tcm Theory

Abstract Background: The Corona Virus Disease 2019 (Covid-19) caused pandemic all over the world. As more and more patients gradually are recovering from Covid-19, they still have some symptoms like short of breath, cough, and phlegm. how to improve their quality of life and shorten the rehabilitation time is still no widely recognized clinical program. In this study, we designed Xiao Tan San Jie (XTSJ) Granule based on traditional Chinese medicine (TCM) theory and assess its efficiency and safety during rehabilitation stage of Covid-19 patients. Method/Design: This study is a 12-week, randomized, double-blinded, controlled, clinical trial that will include 132 Covid-19 patients. Eligible participants will be randomly assigned to XTSJ granule group or placebo group. Participants will receive 28 days treatment. The primary outcome assessment is scores of lung CT scan at week 2 and week 4. The secondary outcome assessment includes pulmonary function test, scores of Visual Analogue Scale (VAS) of Covid-19 symptoms, Scores of Qi Deficiency and Phlegm Stasis syndrome scale, Scores of St. George's Respiratory Questionnaire (SGRQ) at week 2 and week 4. Discussion: In TCM theory XTSJ granule has a regulate effect on respiratory function, lung infection, cough and phlegm which has the potential treatment effect on COVID19 patients. This study will provide initial evidence regarding the efficacy and safety of XTSJ granule for Covid-19 patients in rehabilitation stage. Trial registration: This study was prospectively registered on Chinese Clinical Trial Registry( number: ChiCTR2000031672). Registration date: April 6,2020.

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