Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial
et al., medRxiv, doi:10.1101/2020.07.30.20165365, Aug 2020
HCQ for COVID-19
1st treatment shown to reduce risk in
March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases).
Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper.
Viral load was not measured. As with other studies, PCR may detect non-replicable viral nucleic acid, this is more likely at day 14. Details on the test accuracy are not provided, authors note that RT-PCR sensitivity ranges from 34-80%.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter et al. show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
This study is excluded in the after exclusion results of meta
analysis:
excessive unadjusted differences between groups.
|
risk of progression, 5.0% lower, RR 0.95, p = 1.00, treatment 11 of 349 (3.2%), control 5 of 151 (3.3%), NNT 627.
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risk of progression, 54.8% lower, RR 0.45, p = 0.30, treatment 4 of 31 (12.9%), control 2 of 7 (28.6%), NNT 6.4, with comorbidities.
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risk of viral+ at day 7, 25.5% lower, RR 0.74, p = 0.001, treatment 349, control 151.
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risk of viral+ at day 14, 10.0% higher, RR 1.10, p = 0.52, treatment 349, control 151.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Kamran et al., 4 Aug 2020, prospective, Pakistan, preprint, 10 authors.
Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial
doi:10.1101/2020.07.30.20165365
Background: Hydroxychloroquine (HCQ) has been considered to treat Coronavirus disease 2019 (COVID-19) but data on efficacy is conflicting. we analyzed the efficacy of HCQ) in addition to standard of care (SOC) compared with SOC alone in reducing disease progression in Mild COVID-19
Methods: A single centre open label randomized controlled trial during 10 th April to 31 st May 2020 was conducted at Pak emirates Military Hospital (PEMH) Five hundred patients of both genders having age between 18-80 years with Mild COVID-19 were enrolled. Patients assigned to standard dose of HCQ plus SOC were 349 while 151 patients received SOC (control group). Primary outcome was progression of disease while secondary outcome was PCR negativity on day 7 and 14. The results were analyzed on SPSS version 23. P value <0.05 was considered significant. Results: Median age of intervention group (34 + 11.778 years) and control group (34 + 9.813 years). Disease progressed in 16 patients, 11 (3.15%) were in intervention group as compared to 5 (3.35%) in control group, (P value = 0.865). PCR negativity in intervention and control groups were (day 7, 182 (52.1%) vs. 54 (35.7%) (P value = 0.001), (day 14, 244 (69.9%) vs. 110 (72.8%) (P value = 0.508). Consecutive PCR negativity at day 7 and 14 was observed in 240 (68.8%) in intervention group compared to 108 (71.5%) in control group. (P value = 0.231).
Conclusion: Addition of HCQ to SOC in Mild COVID-19 neither stops disease progression nor help in early and sustained viral clearance.
Conflict of interest statement Manuscript titled "Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial". The authors whose names are mentioned in author list certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
References
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"abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To analyze the efficacy of Hydroxychloroquine (HCQ) plus standard of care (SOC) compared with SOC alone in reducing disease progression in Mild COVID-19</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>A single centre, open label randomized controlled trial</jats:p></jats:sec><jats:sec><jats:title>Place and Duration</jats:title><jats:p>Pulmonology department, Pak emirates Military Hospital (PEMH) from 10 April 2020 to 31 May 2020.</jats:p></jats:sec><jats:sec><jats:title>Methodology</jats:title><jats:p>Five hundred patients of both genders having age between 18-50 years who were PCR positive and had Mild COVID-19 were selected. Patients assigned to standard dose of HCQ (400mg 12 hourly day 1 then 200mg 12 hrly for next 4 days) plus SOC were 349 while 151 patients received SOC comprising of Vit C, Vit D, and Zinc only (control group). Primary outcome was progression of disease while secondary outcome was PCR negativity on day 7 and 14. The results were analyzed on SPSS version 23. P value <0.05 was considered significant.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Median age of intervention group (34 ± 11.778 years) and control group (34 ± 9.813 years). Disease progressed in 16 patients, 11 (3.15%) were in intervention group as compared to 5 (3.35%) in control group, (p value = 0.865). PCR negativity in intervention and control groups were (day 7, 182 (52.1%) vs. 54 (35.7%) (p value = 0.001), (day 14, 244 (69.9%) vs. 110 (72.8%) (p value = 0.508). Consecutive PCR negativity at day 7 and 14 was observed in 240 (68.8%) in intervention group compared to 108 (71.5%) in control group. (p value = 0.231).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Addition of HCQ to standard of care treatment in Mild COVID-19 neither prevents disease progression nor is it significantly associated with successive PCR negativity on day 7 and 14.</jats:p></jats:sec><jats:sec><jats:title>Trial registration</jats:title><jats:p><jats:bold>NCT04491994</jats:bold></jats:p></jats:sec><jats:sec><jats:title>Ethical review of research project</jats:title><jats:p>The research project titled “Clearing the fog: Is HCQ effective in reducing COVID-19 progression” has been reviewed by ethical review committee of Pak Emirates Military Hospital (PEMH) Rawalpindi and got legal and ethical approvals prior to initiation of the research work carried out on subject. All experiments were performed in accordance with the relevant guidelines and regulation. Grant of approval is attached as separate file.</jats:p></jats:sec>",
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Late treatment
is less effective
is less effective
