Table 1.
Hydroxychloroquine-based intervention in the clinical trials as of April 25, 2020
| HCQ/HCQ-Combinations in COVID-19 treatment |
Mechanism | Status | Study | References |
|---|---|---|---|---|
| Hydroxychloroquine (HCQ) |
• Anti-endocytosis of SARS-CoV-2 • Inhibition of TLRs signaling and thereby reduces the formation of pro-inflammatory cytokines |
Phase 1 | • HCQ in outpatient adults with COVID-19 (N= 210) NCT04333654 | (Biot et al. 2006; Vincent et al. 2005; Macfarlane and Manzel 1998; Hacker et al. 1998; Jorge et al. 2018; Sahraei et al. 2020; Wu et al. 2020; Liu and Wang 2020) |
| Phase 2 |
• Healthcare workers prevention of COVID-19 (rate of conversion) (N= 360) NCT04333225 • Prevention and treatment by HCQ (PATCH) (N=400) NCT04329923 |
|||
| Phase 3 |
• For prevention of severe COVID19 (N=1660) NCT04329611 • For the treatment of mild COVID-19 (N=2700) NCT04340544 • Healthcare worker exposure-response and outcomes of HCQ (N=15,000) NCT04334148 • Effect of HCQ on in vivo viral clearance (N= 220) NCT04342221 • Ordinal outcomes scale (N= 510) NCT04332991 • Prevention of COVID-19 (Daily and weekly dosing) (N=3000) NCT04341441 • Prophylaxis (post exposure) (N=1600) NCT04318444 • Prophylaxis (pre exposure) (N=440) NCT04331834 |
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| Phase 4 | • Therapeutic effect of HCQ, ChiCTR2000029559 (N=300), ChiCTR2000029868 (N=360) | |||
| HCQ with chloroquine | Phase 4 | • Therapeutic effects of chloroquine and hydroxychloroquine in severe patients ChiCTR2000029992 (N=100), ChiCTR2000029898 (N=100), ChiCTR2000029899 (N=100) | ||
| Phase 0 | • Mild infection ChiCTR2000030054 (N=100) | |||
|
HCQ, Umifenovir |
• Anti-endocytosis • Inhibition of membrane fusion |
Phase 0 | • Preventive effect of HCQ (N=320) ChiCTR2000029803 | (Zhang et al. 2020) |
|
HCQ, Azithromycin |
• Downregulate cytokines production • Decreases chemotaxis polymorphonuclear-neutrophils to the lungs by IL-8 inhibition • Acceleration neutrophil apoptosis |
Phase 3 | • Comparison HCQ Vs Azithromycin (N= 1550) NCT04334382 | (Amsden 2005; Beigelman et al. 2010; Kanoh and Rubin 2010; Zarogoulidis et al. 2012) |
| Phase 2 |
• Proactive prophylaxis (N= 226) NCT04322396 • Epidemiology of SARS-CoV-2 and Mortality to Covid19 (N=1000) NCT04341207 • Treatment of severe SARS-CoV-2 Infection (N=500) NCT04335552 • HCQ vs Azithromycin activity against Covid-19 (N=300) NCT04329832 |
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|
HCQ, Azithromycin, Vitamins C and D, Zinc |
• Quintuple therapy to treat COVID-19 (N=600) |
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|
HCQ, Lopinavir and ritonavir |
• Interference with Mpro which is a vital enzyme for the SARS-CoV-2 replication | Phase 3 |
•Chemoprophylaxis of COVID-19 (N= 1200) |
(Liu et al. 2020; Adedeji and Sarafianos 2014) |
| Phase 2 |
• Comparison of lopinavir/ritonavir or HCQ (N=150) |
|||
|
HCQ, Sarilumab Baricitinib, Lopinavir/Ritonavir |
• Anti-IL-6 receptor, • Janus kinase inhibitor |
Phase 2 |
• Moderate to severe coronavirus disease COVID-19 (N=1000) |
(Favalli et al. 2020; Fleming 2016; Stebbing et al. 2020; Richardson et al. 2020) |
|
Ciclesonide metered dose inhaler (Alvesco), HCQ |
• Inhibits SARS-CoV-2 RNA replication • Inhibits SARS-CoV-2 cytopathic activity |
• Ciclesonide in mild COVID-19 (N=441) NCT04330586 | (Matsuyama et al. 2020; Jeon et al. 2020) | |
|
Tocilizumab, HCQ, Azithromycin |
• Competitively inhibits IL-6 receptor • Downregulate cytokines production |
• Combined use of HCQ, azithromycin, and tocilizumab (N=276) NCT04332094 | (Fu et al. 2020; Luo et al. 2020) | |
|
HCQ, Remdesivir |
• Inhibits the RNA dependent RNA polymerase | Phase 2, 3 | • Efficacy of different anti-viral drugs (N= 700) NCT04321616 | (Agostini et al. 2018; Brown et al. 2019; de Wit et al. 2020; Ko et al. 2020; Gordon et al. 2020; Warren et al. 2016) |
|
Sarilumab, Azithromycin, HQC |
• Inhibits sIL-6R and mIL-6R receptors | Phase 2,3 | • Immune modulatory drugs and other treatments in COVID-19 (N=60) NCT04341870 | (Lu et al. 2020) |
|
HCQ, Oseltamivir, Azithromycin |
• Neuraminidase inhibitor | Phase 3 | • Therapeutic effect of drug trio (N=5) NCT04338698 | (Mitjà and Clotet 2020) |
|
HCQ, Ascorbic Acid |
• Enhances immune system | Phase 2,3 | • Post-exposure prophylaxis (N=2000) NCT04328961 | (Hemilä 2003; Hemilä and Douglas 1999) |
| Phase 4 | • Newly diagnosed COVID-19 as compared to standard care (N=1250) NCT04334967 | |||
|
Emtricitabine/Tenofovir, Disoproxil, HCQ |
• Reverse transcriptase inhibitor • RNA synthesis inhibitors |
Phase 3 | • Prevention of SARS-CoV-2 infection (N=4000) NCT04334928 | (Duan et al. 2020; Zhu et al. 2020; Deeks 2018) |
N, number of participants in the study; NCT, ClinicalTrials.gov registry number (FDA); ChiCTR, Chinese Clinical Trial Register