scholarly journals Honey and Nigella Sativa in the Prophylaxis of COVID-19; A Randomized Controlled Trial

2021 ◽  
Author(s):  
Sohaib Ashraf ◽  
Shoaib Ashraf ◽  
Rutaba Akmal ◽  
Moneeb Ashraf ◽  
Larab Kalsoom ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Sample Size ◽  
Nigella Sativa ◽  
Risk Exposure ◽  
Medical Institute ◽  
Care Providers ◽  
Post Graduate ◽  
Graduate Medical ◽  
Allocation Ratio

Abstract ObjectivesConsidering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. Trial designThe study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial.ParticipantsAll asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study● High-risk exposure (<6 feet distance for >10min without face protection) ● Moderate exposure (<6 feet distance for >10min with face protection)Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study.Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Intervention and comparatorIn this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan.Main outcomesPrimary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. RandomisationParticipants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. Blinding (masking)Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking.Numbers to be randomised (sample size)1000 participants will be enrolled in the study with 1:1 allocation.Trial StatusThe final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. Trial registrationClinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087.

scholarly journals Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sohaib Ashraf ◽  
Shoaib Ashraf ◽  
Rutaba Akmal ◽  
Moneeb Ashraf ◽  
Larab Kalsoom ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Sample Size ◽  
Study Protocol ◽  
Nigella Sativa ◽  
Risk Exposure ◽  
Community Based ◽  
Post Graduate ◽  
Full Protocol ◽  
Allocation Ratio

Abstract Objectives Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. Trial design The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. Participants All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Intervention and comparator In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. Main outcomes Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. Randomisation Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. Blinding (masking) Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. Numbers to be randomised (sample size) 1000 participants will be enrolled in the study with 1:1 allocation. Trial Status The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. Trial registration Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Implications of a prognostic 40-gene expression profile (40-GEP) test for high-risk cutaneous squamous cell carcinoma (cSCC) on staging-based risk assessment and adjuvant therapy trial design.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22091-e22091
Author(s):  
Chrysalyne Schmults ◽  
Kyle R. Covington ◽  
Sarah J. Kurley ◽  
Robert W. Cook
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
High Risk ◽  
Sample Size ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Trial Design ◽  
Multivariable Analysis ◽  
Primary Objective ◽  
Staging Systems

e22091 Background: Deaths due to cSCC are expected to exceed melanoma-specific deaths. With the demonstration of effective therapies for advanced cSCC, and as treatment of patients in the adjuvant setting is considered, accurate prognosis is critical. For improved identification of ‘high-risk’ patients, with biologically aggressive disease capable of metastasis, a prognostic 40-gene expression profile (40-GEP) test was validated using an independent cohort of patients with high-risk cSCC and known clinical outcomes. The test identified three groups with increasing metastasis risk profiles: Class 1 (low risk), Class 2A (high risk), and Class 2B (highest risk) having metastasis rates of 8.9%, 20.4%, and 60%, respectively. Multivariable analysis demonstrated prognostic efficacy of the 40-GEP test alone and in combination with clinicopathological staging systems. This study evaluated risk stratification with concurrent consideration of the 40-GEP result and the Brigham and Women’s Hospital (BWH) stage. The primary objective was evaluation of the potential impact of the 40-GEP on adjuvant clinical trial design. Methods: To determine if a 40-GEP Class 2B result could optimize clinical trial accrual, metastasis rates of BWH high-risk T stage patients (T2b-T3) alone and in combination with 40-GEP results from the validation cohort were used for two-arm trial sample size calculations. Results: Metastasis rates for cases with T2b-T3 tumors increased from 35.1% to 71.4% when selecting for T2b-T3 cases with a 40-GEP Class 2B result. To provide 80% power to detect hazard ratio of 0.6 with 3 years of follow-up (alpha = 0.05), in line with improvement rates by addition of radiation to surgery, 434 T2b-T3 patients are required for randomization. However, sample size could be reduced by 51% to 214 patients by focusing enrollment on T2b-T3 patients with a 40-GEP Class 2B result. Conclusions: These results support the incorporation of the 40-GEP test into selection processes for patients with T2b-T3 tumors who are at the highest risk for metastasis and appropriate for adjuvant clinical trials.

scholarly journals Comparison of HIV incidence estimated in clinical trial and observational cohort settings in a high risk fishing population in Uganda: Implications for sample size estimates

Vaccine ◽  
2016 ◽  
Vol 34 (15) ◽  
pp. 1778-1785 ◽  
Author(s):  
Andrew Abaasa ◽  
Gershim Asiki ◽  
Matthew A. Price ◽  
Eugene Ruzagira ◽  
Freddie Kibengo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Sample Size ◽  
Hiv Incidence ◽  
Observational Cohort ◽  
Size Estimates

scholarly journals Post-exposure Prophylaxis Against SARS-CoV-2 in Close Contacts of Confirmed COVID-19 Cases (CORIPREV): Study Protocol for a Cluster-randomised Trial

2020 ◽  
Author(s):  
Darrell Tan ◽  
Adrienne K. Chan ◽  
Peter Jüni ◽  
George Tomlinson ◽  
Nick Daneman ◽  
...  
Keyword(s):  
High Risk ◽  
Sample Size ◽  
Randomised Trial ◽  
Sample Size Calculation ◽  
Risk Exposure ◽  
Cluster Randomised Trial ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Exposure Prophylaxis ◽  
The Impact

Abstract Background: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case.Methods: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r versus no intervention, using an adaptive approach to sample size calculation. Participants will be individuals aged >6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35 and 90 include comprehensive epidemiological, clinical, microbiologic and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α=0.05, assuming p0=15%, 5 contacts per case and intra-class correlation coefficient (ICC)=0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Discussion: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection.Trial registration: This trial was registered at www.clinicaltrials.gov (NCT04321174) on March 25, 2020. https://clinicaltrials.gov/ct2/show/NCT04321174

scholarly journals Post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases (CORIPREV): study protocol for a cluster-randomized trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Darrell H. S. Tan ◽  
Adrienne K. Chan ◽  
Peter Jüni ◽  
George Tomlinson ◽  
Nick Daneman ◽  
...  
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Sample Size ◽  
Cluster Randomized Trial ◽  
Risk Exposure ◽  
Post Exposure Prophylaxis ◽  
Primary Analysis ◽  
Cluster Randomized ◽  
Exposure Prophylaxis ◽  
The Impact

Abstract Background Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. Methods This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. Discussion Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. Trial registration This trial was registered at www.ClinicalTrials.gov (NCT04321174) on March 25, 2020.

Planning the Size of Clinical Trials with Allowance for Patient Noncompliance

1990 ◽  
Vol 29 (03) ◽  
pp. 243-246 ◽  
Author(s):  
M. A. A. Moussa
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sample Size ◽  
Event Rate ◽  
Survival Functions ◽  
Time Intervals ◽  
Patient Noncompliance ◽  
Event Rates ◽  
Larger Sample

AbstractVarious approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.

Convergence Insufficiency Treatment Trial – Attention and Reading Trial (CITT-ART): Design and Methods

2015 ◽  
pp. 214-228 ◽  
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Health Care Providers ◽  
Developmental Disorders ◽  
Attention Problems ◽  
Secondary Outcome ◽  
Care Providers ◽  
Treatment Trial ◽  
Additional Hypothesis ◽  
Convergence Insufficiency

Objective: To describe the design and methodology of the Convergence Insufficiency Treatment Trial: Attention and Reading Trial (CITT-ART), the first randomized clinical trial evaluating the effect of vision therapy on reading and attention in school-age children with symptomatic convergence insufficiency (CI). Methods: CITT-ART is a multicenter, placebo-controlled, randomized clinical trial of 324 children ages 9 to 14 years in grades 3 to 8 with symptomatic CI. Participants are randomized to 16 weeks of office-based vergence/accommodative therapy (OBVAT) or placebo therapy (OBPT), both supplemented with home therapy. The primary outcome measure is the change in the Wechsler Individual Achievement Test-Version 3 (WIAT-III) reading comprehension subtest score. Secondary outcome measures are changes in attention as measured by the Strengths and Weaknesses of Attention (SWAN) as reported by parents and teachers, tests of binocular visual function, and other measures of reading and attention. The long-term effects of treatment are assessed 1 year after treatment completion. All analyses will test the null hypothesis of no difference in outcomes between the two treatment groups. The study is entering its second year of recruitment. The final results will contribute to a better understanding of the relationship between the treatment of symptomatic CI and its effect on reading and attention. Conclusion: The study will provide an evidence base to help parents, eye professionals, educators, and other health care providers make informed decisions as they care for children with CI and reading and attention problems. Results may also generate additional hypothesis and guide the development of other scientific investigations of the relationships between visual disorders and other developmental disorders in children.

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