Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia

Mežnar et al., NCT04355026, NCT04355026, Jul 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.

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

No treatment is 100% effective. Protocols combine treatments.

6,300+ studies for 210+ treatments. c19early.org

Meta Analysis

Estimated 90 patient HCQ late treatment RCT with results not reported over 5 years after estimated completion.

37 HCQ RCTs have results missing long after expected1-37
The trials report a total of 20,747 patients, with 11 trials having actual enrollment of 3,487, and the remainder estimated.

Important missing comments or errors? Let us know.

Study covers TMPRSS2 inhibitors, bromhexine, and HCQ.

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. Butler et al., PRINCIPLE: A clinical trial evaluating treatments for suspected and confirmed COVID-19 for recovery at home, PRINCIPLE, www.isrctn.com/ISRCTN86534580isrctn.com.

36. 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.

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

Mežnar et al., 31 Jul 2020, Randomized Controlled Trial, trial NCT04355026 (history).

Late treatment
is less effective