Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
PhD Oriol Mitjà, Marc Corbacho-Monné Bm, Maria Ubals Bm, PhD Cristian Tebe, PhD Judith Peñafiel, PhD Aurelio Tobias, PhD Ester Ballana, Andrea Alemany Bm, Núria Riera-Martí, Bm, Carla A Pérez Bm, PhD Clara Suñer, Pep Laporte Bm, Pol Admella Bm, MBA Jordi Mitjà, MBA Mireia Clua, Laia Bertran Ma, Maria Sarquella Ma, Sergi Gavilán Ba, [ Jordi, Ara Phd, PhD Josep M Argimon, Jordi Casabona, BM Gabriel Cuatrecasas, PhD Paz Cañadas, PhD Aleix Elizalde- Torrent, PhD Robert Fabregat, PhD Magí Farré, Anna Forcada Bm, PhD Gemma Flores-Mateo, MSc Esteve Muntada, MB Núria Nadal, Silvia Narejos, Aroa N Gil-Ortega Bn, Nuria Prat Bm, Jordi Puig Bn, Carles Quiñones Mpharm, PhD Juliana Reyes-Ureña, MSc Ferran Ramírez- Viaplana, PhD Lidia Ruiz, PhD Eva Riveira-Muñoz, Alba Sierra Bn, PhD César Velasco, PhD Rosa Maria Vivanco-Hidalgo, Alexis Sentís, Beiras Phd, PhD Bonaventura Clotet, MD Martí Vall-Mayans
doi:10.1093/cid/ciaa1009/5872589
BACKGROUND: No therapeutics have yet been proven effective for the treatment of mild-illness caused by SARS-CoV-2. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be more efficacious than no-treatment for outpatients with mild Covid-19.
METHODS: We conducted a multicenter, open label, randomized controlled trial in Catalonia (Spain) between March 17, and May 26, 2020. Eligible Covid-19 cases were non-hospitalized adult patients with recently confirmed SARS-CoV-2 infection and less than five days of symptoms. Patients were assigned to receive HCQ (800 mg on day 1, followed by 400 mg once daily for 6 days) or no antiviral treatment (not-placebo controlled). Study outcomes were the reduction of viral RNA load in nasopharyngeal swabs up to 7 days after treatment start, patient disease progression using the WHO scale up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days.
RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD 12.6), mean viral load at baseline was 7.90 (SD 1.82) Log 10 copies/mL, and median time from symptom onset to randomization was 3 days. No significant differences were found in the mean reduction of viral load at day 3 (-1.41 vs. -1.41 Log 10 copies/mL in the control and intervention arm, respectively; difference 0.01 [95% CI -0.28;0.29]) or at day 7 (-3.37 vs. -3.44; d -0.07 [-0.44;0.29]). This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; p = 0.38). No relevant treatment-related AEs were reported.
CONCLUSIONS: In patients with mild Covid-19, no benefit was observed with HCQ beyond the usual care.
A c c e p t e d M a n u s c r i p t 9 concomitant administration of DRV in some participants may have slightly increased plasma levels of HCQ, thereby leading to increased HCQ effect because DRVc is a weak inhibitor of the metabolic enzyme of HCQ, CYP2D6. Therefore, we do not expect the use of DRVc might have reduced the effect of HCQ. Third, owing to the urgency, the trial could not be masked with a placebo, which may affect the rate of AE declared (AEs are less often reported in a control, non-placebo group). Nevertheless, it did not affect the attrition numbers in the control arm. Moreover, to minimize the detection bias of the primary outcome (i.e., the viral load), the laboratory staff remained unaware of participants' allocation. Finally, the regional nature of the trial and overrepresentation of healthcare workers (>80%) may limit the generalization of our findings. Therefore, cautiousness should be taken when extrapolating our data to other countries or settings. HCQ and chloroquine have garnered unprecedented attention as potential therapeutic agents following inconclusive clinical trials in combination or not with azithromycin [9, 12] , uncontrolled case series [14] , and public figure endorsements [28] . While there is a growing body of scientific data against using HCQ for treating Covid-19 that includes a concern for harm, particularly cardiac disease, the potential for the treatment of mild Covid-19 with HCQ has been explored in this trial to provide..
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>No effective treatments for coronavirus disease 2019 (COVID-19) '
'exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be '
'efficacious for outpatients with COVID-19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>Multicenter open-label, randomized, controlled trial conducted in '
'Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with '
'&lt;5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 '
'mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in '
'nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, '
'and time to complete resolution of symptoms. Adverse events were assessed up to 28 '
'days.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>A total of 293 patients were eligible for intention-to-treat '
'analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years '
'(SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time '
'from symptom onset to randomization was 3 days. No differences were found in the mean '
'reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and '
'intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk '
'of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete '
'resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse '
'events were reported.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>In patients with mild COVID-19, no benefit was observed with HCQ '
'beyond the usual care.</jats:p>\n'
' </jats:sec>',
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