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Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.
Ann Intern Med. 2020 10 20; 173(8):623-631.AIM

Abstract

BACKGROUND

No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).

OBJECTIVE

To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.

DESIGN

Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).

SETTING

Internet-based trial across the United States and Canada (40 states and 3 provinces).

PARTICIPANTS

Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.

INTERVENTION

Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.

MEASUREMENTS

Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.

RESULTS

Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).

LIMITATION

Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.

CONCLUSION

Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.

PRIMARY FUNDING SOURCE

Private donors.

Authors+Show Affiliations

University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).Research Institute of the McGill University Health Centre and McGill University, Montréal, Quebec, Canada (M.P.C., E.G.M., T.C.L.).M Health Fairview Investigational Drug Service Pharmacy, Minneapolis, Minnesota (D.L.).University of Manitoba, Winnipeg, Manitoba, Canada (S.A.L., L.J.M., G.D., R.Z.).University of Manitoba, Winnipeg, Manitoba, Canada (S.A.L., L.J.M., G.D., R.Z.).University of Manitoba, Winnipeg, Manitoba, Canada (S.A.L., L.J.M., G.D., R.Z.).George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada (L.E.K.).University of Alberta, Edmonton, Alberta, Canada (I.S.S.).University of Manitoba, Winnipeg, Manitoba, Canada (S.A.L., L.J.M., G.D., R.Z.).Research Institute of the McGill University Health Centre and McGill University, Montréal, Quebec, Canada (M.P.C., E.G.M., T.C.L.).Research Institute of the McGill University Health Centre and McGill University, Montréal, Quebec, Canada (M.P.C., E.G.M., T.C.L.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

32673060

Citation

Skipper, Caleb P., et al. "Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : a Randomized Trial." Annals of Internal Medicine, vol. 173, no. 8, 2020, pp. 623-631.
Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. Ann Intern Med. 2020;173(8):623-631.
Skipper, C. P., Pastick, K. A., Engen, N. W., Bangdiwala, A. S., Abassi, M., Lofgren, S. M., Williams, D. A., Okafor, E. C., Pullen, M. F., Nicol, M. R., Nascene, A. A., Hullsiek, K. H., Cheng, M. P., Luke, D., Lother, S. A., MacKenzie, L. J., Drobot, G., Kelly, L. E., Schwartz, I. S., ... Boulware, D. R. (2020). Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. Annals of Internal Medicine, 173(8), 623-631. https://doi.org/10.7326/M20-4207
Skipper CP, et al. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : a Randomized Trial. Ann Intern Med. 2020 10 20;173(8):623-631. PubMed PMID: 32673060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. AU - Skipper,Caleb P, AU - Pastick,Katelyn A, AU - Engen,Nicole W, AU - Bangdiwala,Ananta S, AU - Abassi,Mahsa, AU - Lofgren,Sarah M, AU - Williams,Darlisha A, AU - Okafor,Elizabeth C, AU - Pullen,Matthew F, AU - Nicol,Melanie R, AU - Nascene,Alanna A, AU - Hullsiek,Kathy H, AU - Cheng,Matthew P, AU - Luke,Darlette, AU - Lother,Sylvain A, AU - MacKenzie,Lauren J, AU - Drobot,Glen, AU - Kelly,Lauren E, AU - Schwartz,Ilan S, AU - Zarychanski,Ryan, AU - McDonald,Emily G, AU - Lee,Todd C, AU - Rajasingham,Radha, AU - Boulware,David R, Y1 - 2020/07/16/ PY - 2020/7/17/pubmed PY - 2020/10/28/medline PY - 2020/7/17/entrez SP - 623 EP - 631 JF - Annals of internal medicine JO - Ann Intern Med VL - 173 IS - 8 N2 - BACKGROUND: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). OBJECTIVE: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668). SETTING: Internet-based trial across the United States and Canada (40 states and 3 provinces). PARTICIPANTS: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset. INTERVENTION: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. MEASUREMENTS: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days. RESULTS: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29). LIMITATION: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages. CONCLUSION: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19. PRIMARY FUNDING SOURCE: Private donors. SN - 1539-3704 UR - https://www.unboundmedicine.com/medline/citation/32673060/full_citation L2 - https://www.acpjournals.org/doi/10.7326/M20-4207?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -