Geographical Representation of Low- and Middle-Income Countries in Randomized Clinical Trials for COVID-19

Ramanan, Mahesh; Tong, Steven Y C; Kumar, Aashish; Venkatesh, Balasubramanian

doi:10.1001/jamanetworkopen.2022.0444

Cited by 11 publications

(7 citation statements)

References 8 publications

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“… 60 This trend continued in COVID-19-related randomized controlled trials (vaccine and non-vaccine) with 84% of participants being recruited from high-income countries. 61 Our study found that while many vaccines in Phase 4 during 2021 employed a global research strategy with clinical trials in more than five countries (75%), the majority of Phase 2/3 (0%) and Phase 3 (12%) vaccines did not.…”

Section: Resultsmentioning

confidence: 62%

Assessment of the COVID-19 vaccine market landscape in 2021 relative to challenges in low- and middle-income countries

Oddleifson

Kayani

Shrivastava

et al. 2022

Human Vaccines & Immunotherapeutics

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To evaluate the early vaccine landscape relative to challenges faced by low- and middle-income countries (LMIC), we conducted a cross-sectional study of all COVID-19 vaccines in clinical trials in 2021 (n = 123) using a structured 13-point analytic framework. Supply sustainability was defined as a composite metric of four manufacturing and regulation variables. Vaccine desirability was defined as a composite metric of nine development and distribution variables. Ten vaccines in phases 2/3, 3, or 4 and five vaccines in phases 1 and 1/2 had a sustainability score equal to or above 0.5. Ten vaccines in phases 2/3, 3, or 4 and seven vaccines in phases 1 and 1/2 had a desirability score equal to or above 0.5. No vaccines in Phases 2/3, 3, or 4 met more than one distribution criterion. Structured assessment COVID-19 vaccine candidates in clinical trials in 2021 revealed numerous challenges to adequate access in LMICs. Key policy recommendations included increasing technology transfer to LMICs, developing international legal mechanisms to prevent export bans, and increasing investment in vaccine candidates with more favorable distribution profiles.

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Section: Resultsmentioning

confidence: 62%

Assessment of the COVID-19 vaccine market landscape in 2021 relative to challenges in low- and middle-income countries

Oddleifson

Kayani

Shrivastava

et al. 2022

Human Vaccines & Immunotherapeutics

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“…26,27 Strengths of this report include selection of a vitamin C regimen based on promising initial evaluations, 19,28 excellent treatment adherence and follow-up, and enhanced generalizability based on enrollment in broad geographic areas. 29…”

Section: Discussionmentioning

confidence: 99%

Intravenous Vitamin C for Patients Hospitalized With COVID-19

Florescu,

Stanciu,

Zaharia

et al. 2023

JAMA

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ImportanceThe efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.ObjectiveTo determine whether vitamin C improves outcomes for patients with COVID-19.Design, Setting, and ParticipantsTwo prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents.InterventionsPatients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses).Main Outcomes and MeasuresThe primary outcome was a composite of organ support–free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from –1 organ support–free days for patients experiencing in-hospital death to 22 organ support–free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support–free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility.ResultsEnrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support–free days was 7 (IQR, −1 to 17 days) for the vitamin C group vs 10 (IQR, −1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support–free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy.Conclusions and RelevanceIn hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support–free days and hospital survival.Trial RegistrationClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP)

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“…Therefore, larger trials that provide evidence of the efficacy of nafamostat mesylate in the treatment of COVID-19 are urgently needed. However, the unascertained viral evolution, the impediments procuring nafamostat for study given the limited number of manufacturers around the world, the logistics of administering a 24-h continuous IV infusion in COVID-19 patients as well as the broader organisational challenges with researching during a global pandemic [ 48 , 49 ] ensure that performing such larger trials for nafamostat is difficult.…”

Section: Discussionmentioning

confidence: 99%

Nafamostat Mesylate for Treatment of COVID-19 in Hospitalised Patients: A Structured, Narrative Review

et al. 2022

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The search for clinically effective antivirals against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is ongoing. Repurposing of drugs licensed for non–coronavirus disease 2019 (COVID-19) indications has been extensively investigated in laboratory models and in clinical studies with mixed results. Nafamostat mesylate (nafamostat) is a drug licensed in Japan and Korea for indications including acute pancreatitis and disseminated intravascular coagulation. It is available only for continuous intravenous infusion. In vitro human lung cell line studies with nafamostat demonstrate high antiviral potency against SARS-CoV-2 (half maximal inhibitory concentration [IC50] of 0.0022 µM [compared to remdesivir 1.3 µM]), ostensibly via inhibition of the cellular enzyme transmembrane protease serine 2 (TMPRSS2) preventing viral entry into human cells. In addition, the established antithrombotic activity is hypothesised to be advantageous given thrombosis-associated sequelae of COVID-19. Clinical reports to date are limited, but indicate a potential benefit of nafamostat in patients with moderate to severe COVID-19. In this review, we will explore the pre-clinical, pharmacokinetic and clinical outcome data presently available for nafamostat as a treatment for COVID-19. The recruitment to ongoing clinical trials is a priority to provide more robust data on the safety and efficacy of nafamostat as a treatment for COVID-19.

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Geographical Representation of Low- and Middle-Income Countries in Randomized Clinical Trials for COVID-19

Abstract: regarding trial sponsor, recruitment by country and other trial characteristics were extracted.

Cited by 11 publications

References 8 publications

Assessment of the COVID-19 vaccine market landscape in 2021 relative to challenges in low- and middle-income countries

Assessment of the COVID-19 vaccine market landscape in 2021 relative to challenges in low- and middle-income countries

Intravenous Vitamin C for Patients Hospitalized With COVID-19

Nafamostat Mesylate for Treatment of COVID-19 in Hospitalised Patients: A Structured, Narrative Review

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