Post-exposure prophylaxis with hydroxychloroquine for the prevention of COVID-19, a myth or a reality? The PEP-CQ Study

Dhibar, Deba Prasad; Arora, Navneet; Kakkar, Arpit; Singla, Neeraj; Mohindra, Ritin; Suri, Vikas; Bhalla, Ashish; Sharma, Navneet; Singh, Mini P.; Prakash, Ajay; Lakshmi, P V M; Medhi, Bikash

doi:10.1016/j.ijantimicag.2020.106224

Cited by 16 publications

(27 citation statements)

References 16 publications

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“…Our findings are consistent with those of a prospective, non-randomized, study 33 in which asymptomatic subjects (non-HCW, mean age 37.2 years) mostly exposed to laboratory confirmed COVID-19 cases could opt to receive HCQ prophylaxis (800 mg first day, then 400 mg weekly for 3 weeks) or standard care alone (control). There was a reduction of the 4-week incidence of Covid-19 associated with HCQ compared with controls (19.4% vs. 10.6%, p=0.033, NNT =12).…”

Section: Discussionsupporting

confidence: 89%

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Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Wiseman

Kory

Saidi

et al. 2020

Preprint

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BACKGROUND: A recent trial (NCT04308668) found that post-exposure prophylaxis with hydroxychloroquine (HCQ) was associated with a reduced incidence of Covid-19 by 17% overall; 36% in younger subjects, 31% in household contacts and 49% given within one day. To understand these trends, we prospectively re-analyzed the released dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying primarily by time to drug receipt, age and gender. RESULTS: Requesting additional data, we found that 52% of subjects received medication 1-2 days after the intended overnight delivery; 19% of them outside the intended four-day window from exposure. After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received up to 3 days (Early) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not later (Late) (RR 1.22, 95%CI 0.72 - 2.04). We found a significant HCQ-associated reduction in subjects 18 to 45 years old associated with Early (RR 0.53, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. There were reductions associated with Early prophylaxis in household contacts (RR 0.35, 95%CI 0.13-0.89; p=0.025, NNT 5.7) and Health Care Workers (RR 0.74, 95%CI 0.4-1.38). We did not detect effects of gender, folate, zinc, or ascorbic acid. CONCLUSIONS: Using novel data with a prospective post hoc re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced illness compatible with Covid-19 or confirmed infection when supplied for post-exposure prophylaxis between 1 and 3 days after high-risk or moderate-risk exposure. This finding warrants prospective confirmation. Registered with the Open Science Framework (last revised September 27, 2020, osf.io/fqtnw).

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Section: Discussionsupporting

confidence: 89%

“…Illustrative of the limitations of the pharmacokinetic model [34] is an Indian non-randomized prospective study. [36] Despite using lower loading and maintenance doses than in the PEP study (Table 5), this study reported a 45% reduction of Covid-19 associated with HCQ at 4 weeks.…”

Section: Findings In the Context Of Other Prophylaxis Studiesmentioning

confidence: 66%

Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Wiseman

Kory

Saidi

et al. 2020

Preprint

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“…Dhibar et al’s study had a longer duration of prophylaxis than the current study, and they reported mild adverse drug reactions in patients who received HCQ. They also included healthcare workers, and their study population was diverse ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19

Shabani

Totonchi

Rezaeimirghaed

et al. 2021

Pulmonary Pharmacology & Therapeutics

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Introduction The coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality worldwide. The disease attacks the lung tissue and may lead to acute respiratory distress syndrome. An in vitro study showed that hydroxychloroquine (HCQ) has a prophylactic effect against COVID-19 due to its anti-inflammatory effects. The present study aimed to evaluate the prophylactic effect of HCQ on individuals in close contact with patients with COVID-19. Method In this quasi-trial study, we prescribed HCQ for 7 days to all people who had close contact with a patient with COVID-19. All contacts underwent a nasal swab in two steps, and those positive for COVID-19 were excluded from the study. After 14 days of follow-up, the clinical and laboratory manifestations of COVID-19 were evaluated. Results A total of 113 participants completed the study. The HCQ group comprised 51 (45.13 %) contacts, and 62 (54.86 %) contacts were allocated to the control group. According to the results of clinical examination and real-time polymerase chain reaction test, 8 (12.90%) contacts in the control group were reported to have contracted COVID-19. In the HCQ group, 7 (13.72%) contacts were confirmed to have contracted COVID-19. There was no relationship between HCQ use and age, sex, underlying disorders, and laboratory data (all p >0.05). In terms of HCQ side effects, five participants experienced gastrointestinal and cutaneous side effects that subsided on discontinuation of HCQ. Conclusion The current study showed that HCQ had no prophylactic effect with regard to COVID-19 prevention.

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“…19 In a trial evaluating the e cacy of HCQ and standard of care vs standard of care alone, Tang and colleagues showed that the addition of HCQ did not result in a signi cantly higher probability of negative PCR conversion by 28 days. 20 In outpatient settings, HCQ has also shown mixed e cacy when used as postexposure prophylaxis with one study in India showing a relative reduction in the incidence of COVID-19 21 while two other trials in the United States and Canada did not demonstrate any bene t in prevention of COVID-19. 22 23 Further, the use of once or twice weekly or daily (over 8 weeks) HCQ as pre-exposure prophylaxis among health care workers did not signi cantly reduce the incidence of laboratory con rmed SARS-CoV-2 infection.…”

Section: Safety Of Hcqmentioning

confidence: 99%

Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial

Byakika-Kibwika

Sekaggya-Wiltshire

Semakula

et al. 2021

Preprint

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BackgroundSeveral repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DesignWe conducted a randomized open label Phase II clinical trial from October -December 2020.MethodsPatients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6.ResultsOf the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p=0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group.ConclusionOur results show that HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution. Trial registration: NCT04860284

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Post-exposure prophylaxis with hydroxychloroquine for the prevention of COVID-19, a myth or a reality? The PEP-CQ Study

Cited by 16 publications

References 16 publications

Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19

Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial

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