Ongoing trials with TKIs in treatment of COVID-19
| Class/agent . | Goal . | Comments . |
|---|---|---|
| BTK | ||
| Ibrutinib | Efficacy in reducing respiratory failure | Quadruple-blind RCT, NCT04375397 |
| Efficacy in reducing respiratory failure and preventing death | Double-blind RCT, NCT04439006 | |
| Acalabrutinib | Efficacy in preventing deterioration, mortality, and respiratory failure or speeding up recovery of hospitalized patients with COVID-19 | Multiarm RCT, 2020-001736-95 (ACCORD 2) |
| Zanubrutinib | Efficacy in increasing proportion of respiratory failure-free patients | Double-blind RCT, NCT04382586 |
| SYK | ||
| Fostamatinib | Efficacy in reducing mortality, SAEs, inflammatory biomarkers, and hospital admission | RCT, 2020-001750-22 |
| Efficacy in preventing progression to severe/critical disease | Double-blind RCT, NCT04629703 | |
| BCR-Abl | ||
| Imatinib | Efficacy in preventing vascular leak | Single blind-RCT, 2020-001236-10 |
| Efficacy of baricitinib, imatinib, or lopinavir in combination with hydroxychloroquine | RCT, 2020-001321-31 | |
| Efficacy in preventing need for invasive mechanical ventilation | RCT, NCT04422678 | |
| Safety and efficacy in hospitalized adults | Double-blind RCT, NCT04394416 | |
| Time to clinical improvement with treatment with hydroxychloroquine in combination with baricitinib, imatinib, or lopinavir/ritonavir | RCT, 2020-001321-31 | |
| Time to clinical improvement | RCT, NCT04346147 | |
| Efficacy in preventing severe COVID-19 in hospitalized aged patients | RCT, NCT04357613 | |
| PI3K/mTOR | ||
| Duvelisib | Overall survival, length of hospital/ICU stay | Triple-blind RCT, NCT04372602 |
| Efficacy in requirement for mechanical ventilation or dying | Double-blind RCT, NCT04487886 | |
| Temsirolimus | Efficacy in preventing respiratory failure | Double-blind RCT, NCT04482712 |
| Time to clinical recovery and viral clearance | Single-blind RCT, NCT04461340 | |
| Proportion of patients alive and free from advanced respiratory support measures | Quadruple-blind RCT, NCT04341675 | |
| JAK | ||
| Ruxolitinib | Efficacy in reducing mortality, SAEs, inflammatory biomarkers, and hospital admission | RCT, 2020-001750-22 |
| Incidence of SAEs and severe disease, safety | Single arm, NCT04348071 | |
| Efficacy in preventing clinical worsening of respiratory status | Single arm, NCT04414098 | |
| Treatment of cytokine storm | Open label, NCT04355793 | |
| Efficacy in preventing death and influencing SAEs/ICU-free days | Double-blind RCT, NCT04377620 | |
| Recovery from pneumonia | Open label, NCT04334044 | |
| Efficacy in reducing respiratory failure and ICU care and preventing death | Double-blind RCT, NCT04362137, NCT04337359 | |
| Reduction of cytokine load by single plasma volume exchanges, with or without ruxolitinib | Open label, NCT04374149 | |
| Efficacy in reversing hyperinflammation (CIS) | Open label, NCT04338958 | |
| Efficacy in preventing death, ICU admission, or mechanical ventilation | Triple-blind RCT, NCT04477993 | |
| Efficacy in preventing SAEs and COVID-19 patients from becoming critically ill | Single arm, NCT04331665 | |
| Overall survival | Open label, NCT04359290 | |
| Efficacy in preventing severe respiratory failure and reducing ICU/hospital stay and survival, in combination with simvastatin | Open label, NCT04348695 | |
| Ability to prevent all-cause mortality, noninvasive or invasive ventilation | Double-blind RCT, NCT04581954 | |
| Ability to achieve a change from baseline in the clinical assessment score COVID-19 with colchicine, ruxolitinib, secukinumab, or standard treatment | Open label, NCT04403243 | |
| Safety and efficacy of ruxolitinib combined with mesenchymal stem cells | Single-blind RCT, ChiCTR2000029580 | |
| Efficacy and safety in patients on respiratory support or approaching need for respiratory support | Open label, 2020-001459-42 | |
| Efficacy of anakinra/tocilizumab, alone or in combination with ruxolitinib, in increasing ventilation-free days | Open-label RCT, 2020-001754-21, NCT04424056 | |
| Clinical and biological efficacy of anakinra, alone or in combination with ruxolitinib, in reducing oxygen dependency, need for invasive ventilation, and systemic inflammation | Open-label RCT, 2020-001963-10 | |
| Efficacy in preventing deterioration requiring mechanical ventilation | Open label, 2020-001777-71 | |
| Overall survival after 28 d | Single arm, 2020-001732-10 | |
| Pacritinib | Efficacy in preventing mechanical ventilation or ECMO | Double-blind RCT, NCT04404361 |
| Class/agent . | Goal . | Comments . |
|---|---|---|
| BTK | ||
| Ibrutinib | Efficacy in reducing respiratory failure | Quadruple-blind RCT, NCT04375397 |
| Efficacy in reducing respiratory failure and preventing death | Double-blind RCT, NCT04439006 | |
| Acalabrutinib | Efficacy in preventing deterioration, mortality, and respiratory failure or speeding up recovery of hospitalized patients with COVID-19 | Multiarm RCT, 2020-001736-95 (ACCORD 2) |
| Zanubrutinib | Efficacy in increasing proportion of respiratory failure-free patients | Double-blind RCT, NCT04382586 |
| SYK | ||
| Fostamatinib | Efficacy in reducing mortality, SAEs, inflammatory biomarkers, and hospital admission | RCT, 2020-001750-22 |
| Efficacy in preventing progression to severe/critical disease | Double-blind RCT, NCT04629703 | |
| BCR-Abl | ||
| Imatinib | Efficacy in preventing vascular leak | Single blind-RCT, 2020-001236-10 |
| Efficacy of baricitinib, imatinib, or lopinavir in combination with hydroxychloroquine | RCT, 2020-001321-31 | |
| Efficacy in preventing need for invasive mechanical ventilation | RCT, NCT04422678 | |
| Safety and efficacy in hospitalized adults | Double-blind RCT, NCT04394416 | |
| Time to clinical improvement with treatment with hydroxychloroquine in combination with baricitinib, imatinib, or lopinavir/ritonavir | RCT, 2020-001321-31 | |
| Time to clinical improvement | RCT, NCT04346147 | |
| Efficacy in preventing severe COVID-19 in hospitalized aged patients | RCT, NCT04357613 | |
| PI3K/mTOR | ||
| Duvelisib | Overall survival, length of hospital/ICU stay | Triple-blind RCT, NCT04372602 |
| Efficacy in requirement for mechanical ventilation or dying | Double-blind RCT, NCT04487886 | |
| Temsirolimus | Efficacy in preventing respiratory failure | Double-blind RCT, NCT04482712 |
| Time to clinical recovery and viral clearance | Single-blind RCT, NCT04461340 | |
| Proportion of patients alive and free from advanced respiratory support measures | Quadruple-blind RCT, NCT04341675 | |
| JAK | ||
| Ruxolitinib | Efficacy in reducing mortality, SAEs, inflammatory biomarkers, and hospital admission | RCT, 2020-001750-22 |
| Incidence of SAEs and severe disease, safety | Single arm, NCT04348071 | |
| Efficacy in preventing clinical worsening of respiratory status | Single arm, NCT04414098 | |
| Treatment of cytokine storm | Open label, NCT04355793 | |
| Efficacy in preventing death and influencing SAEs/ICU-free days | Double-blind RCT, NCT04377620 | |
| Recovery from pneumonia | Open label, NCT04334044 | |
| Efficacy in reducing respiratory failure and ICU care and preventing death | Double-blind RCT, NCT04362137, NCT04337359 | |
| Reduction of cytokine load by single plasma volume exchanges, with or without ruxolitinib | Open label, NCT04374149 | |
| Efficacy in reversing hyperinflammation (CIS) | Open label, NCT04338958 | |
| Efficacy in preventing death, ICU admission, or mechanical ventilation | Triple-blind RCT, NCT04477993 | |
| Efficacy in preventing SAEs and COVID-19 patients from becoming critically ill | Single arm, NCT04331665 | |
| Overall survival | Open label, NCT04359290 | |
| Efficacy in preventing severe respiratory failure and reducing ICU/hospital stay and survival, in combination with simvastatin | Open label, NCT04348695 | |
| Ability to prevent all-cause mortality, noninvasive or invasive ventilation | Double-blind RCT, NCT04581954 | |
| Ability to achieve a change from baseline in the clinical assessment score COVID-19 with colchicine, ruxolitinib, secukinumab, or standard treatment | Open label, NCT04403243 | |
| Safety and efficacy of ruxolitinib combined with mesenchymal stem cells | Single-blind RCT, ChiCTR2000029580 | |
| Efficacy and safety in patients on respiratory support or approaching need for respiratory support | Open label, 2020-001459-42 | |
| Efficacy of anakinra/tocilizumab, alone or in combination with ruxolitinib, in increasing ventilation-free days | Open-label RCT, 2020-001754-21, NCT04424056 | |
| Clinical and biological efficacy of anakinra, alone or in combination with ruxolitinib, in reducing oxygen dependency, need for invasive ventilation, and systemic inflammation | Open-label RCT, 2020-001963-10 | |
| Efficacy in preventing deterioration requiring mechanical ventilation | Open label, 2020-001777-71 | |
| Overall survival after 28 d | Single arm, 2020-001732-10 | |
| Pacritinib | Efficacy in preventing mechanical ventilation or ECMO | Double-blind RCT, NCT04404361 |
CIS, chronic inflammation score; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; RCT, randomized controlled trial; SAE, serious adverse event.