HCQ for COVID-19

1st treatment shown to reduce risk in March 2020, now with p < 0.0000000001 from 426 studies, used in 59 countries.

Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance. 

No treatment is 100% effective.
Protocols combine treatments.

c19early.org

Meta-analysis

Estimated 110 patient HCQ nebulized late treatment RCT with results not reported over 4 years after estimated completion.

37 HCQ RCTs have results missing long after expected1-37
The trials report a total of 20,499 patients, with 12 trials having actual enrollment of 3,639, and the remainder estimated.

Important missing comments or errors? Let us know.

1. Genton et al., #StayHome: Early Hydroxychloroquine to Reduce Secondary Hospitalisation and Household Transmission in COVID-19 (#StayHome), NCT04385264, clinicaltrials.gov/study/NCT04385264clinicaltrials.gov.

2. Hawari et al., The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19, NCT05113810, clinicaltrials.gov/study/NCT05113810clinicaltrials.gov.

3. Ghanem-Zoubi et al., Hydroxychloroquine Post-Exposure Prophylaxis for Coronavirus Disease (COVID-19) Among Health-Care Workers, NCT04438837, clinicaltrials.gov/study/NCT04438837clinicaltrials.gov.

4. Gagneux-Brunon et al., Acceptability of a COVID-19 pre-exposure prophylaxis trial with hydroxychloroquine in French healthcare workers during the first wave of COVID-19 pandemic, Trials, doi:10.1186/s13063-021-05329-y.biomedcentral.com, doi.org.

5. Pineda et al., Prevention and Treatment With Hydroxychloroquine + Azithromycin of Acute Respiratory Syndrome Induced by COVID-19 (AMBUCOV), NCT04954040, clinicaltrials.gov/study/NCT04954040clinicaltrials.gov.

6. Aston et al., Hydroxychloroquine vs. Azithromycin for Outpatients in Utah With COVID-19 (HyAzOUT), NCT04334382, clinicaltrials.gov/study/NCT04334382clinicaltrials.gov.

7. Al Ansari et al., Post Exposure Prophylaxis in Healthcare Workers Exposed to COVID-19 Patients (HCQ-COVID19), NCT04437693, clinicaltrials.gov/study/NCT04437693clinicaltrials.gov.

8. Abayomi et al., A multi-centre, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir for the treatment of COVID-19 in Lagos State: study protocol for a randomized controlled trial, Trials, doi:10.1186/s13063-021-05675-x.biomedcentral.com, doi.org.

9. González et al., Hydroxychloroquine efficacy and safety in preventing SARS-CoV-2 infection and COVID-19 disease severity during pregnancy (COVID-Preg): a structured summary of a study protocol for a randomised placebo controlled trial, Trials, doi:10.1186/s13063-020-04557-y.biomedcentral.com, doi.org.

10. Nanni et al., PROTECT Trial: A cluster-randomized study with hydroxychloroquine versus observational support for prevention or early-phase treatment of Coronavirus disease (COVID-19): A structured summary of a study protocol for a randomized controlled trial, Trials, doi:10.1186/s13063-020-04527-4.biomedcentral.com, doi.org.

11. Granados-Montiel et al., New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial), BMJ Open, doi:10.1136/bmjopen-2020-045190.bmj.com, doi.org.

12. Kara et al., Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19, NCT04411433, clinicaltrials.gov/study/NCT04411433clinicaltrials.gov.

13. Chauffe et al., Hydroxychloroquine as Prophylaxis for COVID-19 in Healthcare Workers (HCQPreP), NCT04363450, clinicaltrials.gov/study/NCT04363450clinicaltrials.gov.

14. Moraes et al., Comparative Study of Hydroxychloroquine and Ivermectin in COVID-19 Prophylaxis, NCT04384458, clinicaltrials.gov/study/NCT04384458clinicaltrials.gov.

15. Borrie et al., COVID-19 PEP- High-risk Individuals in Long-term and Specialized Care - Canada, NCT04397328, clinicaltrials.gov/study/NCT04397328clinicaltrials.gov.

16. James et al., PROLIFIC ChemoprophylaxisTrial (COVID-19), NCT04352933, clinicaltrials.gov/study/NCT04352933clinicaltrials.gov.

17. Morales-Asencio et al., Prevention of COVID19 Infection in Nursing Homes by Chemoprophylaxis With Hydroxychloroquine, NCT04400019, clinicaltrials.gov/study/NCT04400019clinicaltrials.gov.

18. Mordmüller et al., Hydroxychloroquine for COVID-19 (COV-HCQ), NCT04342221, clinicaltrials.gov/study/NCT04342221clinicaltrials.gov.

19. Gül et al., Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment, NCT04981379, clinicaltrials.gov/study/NCT04981379clinicaltrials.gov.

20. Abu-Helalah et al., Chemoprevention Clinical Trial of COVID-19: Hydroxychloroquine Post Exposure Prophylaxis (APCC-19), NCT04597775, clinicaltrials.gov/study/NCT04597775clinicaltrials.gov.

21. Okasha et al., Hydroxychloroquine and Nitazoxanide Combination Therapy for COVID-19, NCT04361318, clinicaltrials.gov/study/NCT04361318clinicaltrials.gov.

22. Levi et al., Open Label Study to Compare Efficacy, Safety and Tolerability of Hydroxychloroquine Combined With Azithromycin Compared to Hydroxychloroquine Combined With Camostat Mesylate and to "no Treatment" in SARS CoV 2 Virus (COSTA), NCT04355052, clinicaltrials.gov/study/NCT04355052clinicaltrials.gov.

23. WellStar, Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease, NCT04429867, clinicaltrials.gov/study/NCT04429867clinicaltrials.gov.

24. Burney et al., Hydroxychloroquine Chemoprophylaxis for COVID-19 Infection in High-risk Healthcare Workers, NCT04370015, clinicaltrials.gov/study/NCT04370015clinicaltrials.gov.

25. Sow et al., Phytomedicines Versus Hydroxychloroquine as an Add on Therapy to Azithromycin in Asymptomatic Covid-19 Patients (PHYTCOVID-19), NCT04501965, clinicaltrials.gov/study/NCT04501965clinicaltrials.gov.

26. Pellegrini et al., Effectiveness of Prophylactic Hydroxychloroquine on incidence of COVID-19 infection in Front-line Health and Allied Health Care Workers: The COVID-SHIELD Trial, COVID-SHIELD, ACTRN12620000501943, www.anzctr.org.au/TrialSearch.aspx#&&conditionCode=&dateOfRegistrationFrom=&interventionDescription=&interventionCodeOperator=OR&primarySponsorType=&gender=&distance=&postcode=&pageSize=20&ageGroup=&recruitmentCountryOperator=OR&recruitmentRegion=ðicsReview=&countryOfRecruitment=Australia%7cNew+Zealand®istry=&searchTxt=ACTRN12620000501943org.au.

27. Sarwar et al., Post-Exposure Prophylaxis for Asymptomatic SARS-CoV-2 COVID-19 Patients With Choloroquine Compounds (PEACE), NCT04346667, clinicaltrials.gov/study/NCT04346667clinicaltrials.gov.

28. Sarwar (B) et al., Prophylaxis of Exposed COVID-19 Individuals With Mild Symptoms Using Choloroquine Compounds (PRECISE), NCT04351191, clinicaltrials.gov/study/NCT04351191clinicaltrials.gov.

29. Connor et al., HEalth Care Worker pROphylaxis Against COVID-19: The HERO Trial (HERO), NCT04352946, clinicaltrials.gov/study/NCT04352946clinicaltrials.gov.

30. El-Sherbiny et al., Development and Validation of "Ready-to-Use" Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19, NCT04477083, clinicaltrials.gov/study/NCT04477083clinicaltrials.gov.

31. Ajili et al., A Study of Hydroxychloroquine and Zinc in the Prevention of COVID-19 Infection in Military Healthcare Workers (COVID-Milit), NCT04377646, clinicaltrials.gov/study/NCT04377646clinicaltrials.gov.

32. Mežnar et al., Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia, NCT04355026, clinicaltrials.gov/study/NCT04355026clinicaltrials.gov.

33. Niriella et al., Hydroxychloroquine for post-exposure prophylaxis of COVID-19 among naval personnel in Sri Lanka: study protocol for a randomized, controlled trial, Trials, doi:10.1186/s13063-020-04659-7.biomedcentral.com, doi.org.

34. Farooq et al., Effectiveness of Hydroxychloroquine in Covid-19 Patients (Covid), NCT04328272, clinicaltrials.gov/study/NCT04328272clinicaltrials.gov.

35. Treluyer et al., Prevention of SARS-CoV-2 in Hospital Workers s Exposed to the Virus (PREP-COVID), PREP-COVID, NCT04344379, clinicaltrials.gov/study/NCT04344379clinicaltrials.gov.

36. Borba et al., Phase IIb Study to Evaluate the Efficacy and Safety of Chloroquine Diphosphate in the Treatment of Patients With Comorbidities, Without Severe Acute Respiratory Syndrome, Under the New Coronavirus (SARS-CoV2): a Double-blind, Randomized, Placebo-controlled Clinical Trial, NCT04342650, clinicaltrials.gov/study/NCT04342650clinicaltrials.gov.

37. Kim et al., Comparison of Lopinavir/Ritonavir or Hydroxychloroquine in Patients With Mild Coronavirus Disease (COVID-19), NCT04307693, clinicaltrials.gov/study/NCT04438837clinicaltrials.gov.

Hawari et al., 20 Jul 2022, Randomized Controlled Trial, trial NCT05113810 (history). Contact: YD.14502@KHCC.JO.

Late treatment
is less effective

Most accessed treatments

Antiviral effects

Vitamins & Minerals

Host endosomal entry / trafficking

Dual-action mAbs

RdRp

Nasal & Oral Sprays / Rinses

Analgesics

Antiandrogens

Host targets and pathways

Inflammatory and immune modulation

Mpro (Gen 1)

Oxidative stress and cytoprotection

Lifestyles

TMPRSS2

Spike neutralization

Replication inhibition (target unresolved)

COVID-19 mAbs

Pleiotropic modulation

Attachment / entry inhibition

Mpro (Gen 2)

H1RAs

Nutrients and microbiome support

Host mAbs

IL-6 / IL-6R blockade

Physical and extracorporeal interventions

Natural products and extracts

Symptom management

Unconfirmed antiviral rationale

Lifestyle, behaviors, and exposure prevention

Other complication management

Mpro / 3CLpro

Host pyrimidine synthesis

Direct viral inactivation

Endothelial / vascular protection

Direct respiratory tract treatments

Other antibodies, proteins, peptides, cells, and RNA therapies

Secondary infection and coinfection management

The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19

HCQ for COVID-19