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Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial

BACKGROUND & OBJECTIVES: Chloroquine (CQN) administered as nasal drops has the potential to achieve much greater local tissue levels than with oral/systemic administration. This trial was undertaken to study the efficacy and safety profile of topical nasal administration of CQN drops in reducing...

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Autores principales: Thakar, Alok, Panda, Smriti, Sakthivel, Pirabu, Brijwal, Megha, Dhakad, Shivram, Choudekar, Avinash, Kanodia, Anupam, Bhatnagar, Sushma, Mohan, Anant, Maulik, Subir K., Dar, Lalit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184066/
https://www.ncbi.nlm.nih.gov/pubmed/33818472
http://dx.doi.org/10.4103/ijmr.IJMR_3665_20
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author Thakar, Alok
Panda, Smriti
Sakthivel, Pirabu
Brijwal, Megha
Dhakad, Shivram
Choudekar, Avinash
Kanodia, Anupam
Bhatnagar, Sushma
Mohan, Anant
Maulik, Subir K.
Dar, Lalit
author_facet Thakar, Alok
Panda, Smriti
Sakthivel, Pirabu
Brijwal, Megha
Dhakad, Shivram
Choudekar, Avinash
Kanodia, Anupam
Bhatnagar, Sushma
Mohan, Anant
Maulik, Subir K.
Dar, Lalit
author_sort Thakar, Alok
collection PubMed
description BACKGROUND & OBJECTIVES: Chloroquine (CQN) administered as nasal drops has the potential to achieve much greater local tissue levels than with oral/systemic administration. This trial was undertaken to study the efficacy and safety profile of topical nasal administration of CQN drops in reducing viral load and preventing clinical progression in early COVID-19 infection. METHODS: This randomized clinical trial was done with a sample size of 60. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed asymptomatic patients or those with mild COVID-19 illness [National Early Warning Score (NEWS) ≤4] were included. Patients were randomized in a 1:1 manner. Control arm (standard supportive treatment, n=30) was compared with intervention arm (n=30) of standard treatment plus CQN eye drops (0.03%) repurposed as nasal drops administered six times daily (0.5 ml/dose) for 10 days. Outcome measures were adverse events and adherence; clinical progression and outcomes were measured by NEWS; sequential RT-PCR cycle threshold (Ct) values were also noted on days 0, 3, 7 and 10. RESULTS: Nasal CQN was associated with local irritation in seven and non-compliance in one of 30 patients. Eleven patients were excluded due to enrolment error (2 – recovered; 9 – false-positive referral), and 49 patients were analyzed as per modified intention-to-treat analysis. Clinical recovery was noted as similar with 100 per cent asymptomatic by day seven in both arms. Virological outcomes also indicated similarly improving Ct values in both arms, and similar proportion of patients transitioning to non-infectivity by day 10 (controls - 19/25; nasal CQN - 15/24). Nine false-positive patients with enrolment error and day 0 RT-PCR negative were initially uninfected but had continuing COVID-19 exposure and treatment as per randomization. Patients receiving nasal CQN (n=5) demonstrated stable Ct values from day 0 to 10, while patients with no nasal CQN (n=4) demonstrated significant dip in Ct value indicating to infection (Ct<35) and infectivity (Ct<33). INTERPRETATION & CONCLUSIONS: The present study suggests to the potential of topical nasal CQN in the prevention of COVID-19 infection if administered before the infection is established. No significant differences in clinical or virological outcome were however, demonstrated in patients with mild but established illness.
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spelling pubmed-81840662021-06-21 Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial Thakar, Alok Panda, Smriti Sakthivel, Pirabu Brijwal, Megha Dhakad, Shivram Choudekar, Avinash Kanodia, Anupam Bhatnagar, Sushma Mohan, Anant Maulik, Subir K. Dar, Lalit Indian J Med Res Original Article BACKGROUND & OBJECTIVES: Chloroquine (CQN) administered as nasal drops has the potential to achieve much greater local tissue levels than with oral/systemic administration. This trial was undertaken to study the efficacy and safety profile of topical nasal administration of CQN drops in reducing viral load and preventing clinical progression in early COVID-19 infection. METHODS: This randomized clinical trial was done with a sample size of 60. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed asymptomatic patients or those with mild COVID-19 illness [National Early Warning Score (NEWS) ≤4] were included. Patients were randomized in a 1:1 manner. Control arm (standard supportive treatment, n=30) was compared with intervention arm (n=30) of standard treatment plus CQN eye drops (0.03%) repurposed as nasal drops administered six times daily (0.5 ml/dose) for 10 days. Outcome measures were adverse events and adherence; clinical progression and outcomes were measured by NEWS; sequential RT-PCR cycle threshold (Ct) values were also noted on days 0, 3, 7 and 10. RESULTS: Nasal CQN was associated with local irritation in seven and non-compliance in one of 30 patients. Eleven patients were excluded due to enrolment error (2 – recovered; 9 – false-positive referral), and 49 patients were analyzed as per modified intention-to-treat analysis. Clinical recovery was noted as similar with 100 per cent asymptomatic by day seven in both arms. Virological outcomes also indicated similarly improving Ct values in both arms, and similar proportion of patients transitioning to non-infectivity by day 10 (controls - 19/25; nasal CQN - 15/24). Nine false-positive patients with enrolment error and day 0 RT-PCR negative were initially uninfected but had continuing COVID-19 exposure and treatment as per randomization. Patients receiving nasal CQN (n=5) demonstrated stable Ct values from day 0 to 10, while patients with no nasal CQN (n=4) demonstrated significant dip in Ct value indicating to infection (Ct<35) and infectivity (Ct<33). INTERPRETATION & CONCLUSIONS: The present study suggests to the potential of topical nasal CQN in the prevention of COVID-19 infection if administered before the infection is established. No significant differences in clinical or virological outcome were however, demonstrated in patients with mild but established illness. Wolters Kluwer - Medknow 2021 /pmc/articles/PMC8184066/ /pubmed/33818472 http://dx.doi.org/10.4103/ijmr.IJMR_3665_20 Text en Copyright: © 2021 Indian Journal of Medical Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Original Article
Thakar, Alok
Panda, Smriti
Sakthivel, Pirabu
Brijwal, Megha
Dhakad, Shivram
Choudekar, Avinash
Kanodia, Anupam
Bhatnagar, Sushma
Mohan, Anant
Maulik, Subir K.
Dar, Lalit
Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
title Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
title_full Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
title_fullStr Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
title_full_unstemmed Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
title_short Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
title_sort chloroquine nasal drops in asymptomatic & mild covid-19: an exploratory randomized clinical trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184066/
https://www.ncbi.nlm.nih.gov/pubmed/33818472
http://dx.doi.org/10.4103/ijmr.IJMR_3665_20
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