Table 2.
A list of clinical trials investigating the efficacies of therapeutic approaches in COVID-19.
| Drug | Mechanism | No. | Phase | Status | Aim and outcome | Identifier | |
|---|---|---|---|---|---|---|---|
| Monoclonal Abs | |||||||
| Tocilizumab | mAb against IL-6 | 243 | Phase 3 | Completed | This is a randomized, double blind, multi-center study to evaluate the effects of tocilizumab compared to placebo on the multi-organ dysfunction and outcomes of hospitalized patients with COVID-19. | NCT04356937 | |
| Sarilumab | mAb against IL-6 | 420 | Phase 3 | Completed | An adaptive Phase 3, randomized, double-blind, placebo-controlled study to assess efficacy and safety of Sarilumab in adult patients hospitalized with severe or critical COVID-19. | NCT04327388 | |
| Siltuximab(Sylvant) | IL-6 neutralization | 220 | NA | Completed | This observational study evaluated efficacy and safety of Siltuximab for treatment of SARS-CoV-2 infection complicated with serious respiratory complications. | NCT04322188 | |
| Canakinumab | IL-1R antagonist | 451 | Phase 3 | Completed | This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of Canakinumab-plus-SOC in patients with COVID-19-induced pneumonia and CRS. | NCT04362813 | |
| Anakinra | IL-1R antagonist | 80 | Phase 2 | Recruiting | Anakinra had showed survival benefits in MAS and sepsis and showed promising outcomes for the use in COVID-19. | NCT04643678 | |
| Anakinra | IL-1R antagonist | 170 | Phase 2 | Not yet recruiting | This study will determine the efficacy of IL-1R blockade in reducing the need for mechanical ventilation and/or 28-day mortality among patients with COVID-19 who have features of CSS and severe respiratory failure. | NCT04603742 | |
| BMS-986253 | Anti-IL-8 | 138 | Phase 2 | Recruiting | This is the first in-human study to evaluate whether neutralizing IL-8 with BMS-986253 can help improve the health condition of severe hospitalized COVID-19 patients. | NCT04347226 | |
| Infliximab | TNFα blocker | 17 | Phase 2 | Completed | This is a prospective, single center, phase 2 trial to assess the efficacy of TNFα inhibitor therapy in hospitalized adult patients with severe or critical COVID-19. | NCT04425538 | |
| AMY-101 | C3 Inhibitor | 144 | Phase 2 | Not yet recruiting | This study will assess the efficacy and safety, as well as PK and PD of AMY-101 in patients with severe COVID-19. | NCT04395456 | |
| Eculizumab | C5 Inhibitor | NA | NA | Available | Eculizumab will be used to modulate the activity of the distal complement preventing the formation of MAC. By this, mortality can be halted while the patient has time to recover from the virus with supportive medical care. | NCT04288713 | |
| Vilobelimab (IFX-1) | anti-C5a antibody | 390 | Phase 2/3 | Recruiting | Consists of i) Phase 2, open-label, randomized evaluating BSC + IFX-1 (Arm A) and BSC alone (Arm B); ii) Phase 3, double-blind, placebo-controlled, randomized comparing SOC + IFX-1 (Arm A) and SOC + placebo-to-match (Arm B). | NCT04333420 | |
| Cenicriviroc (CVC) | CCR2/CCR5 Inhibitor | 183 | Phase 2 | Recruiting | To evaluate the safety and efficacy of Cenicriviroc to reduce the severity of COVID-19. Also, to test if patients with pre-existing conditions, who have an increased risk of severe COVID-19 progression, benefit more. | NCT04500418 | |
| Maraviroc | CCR5 antagonists | 9 | Phase 1 | Completed | This study seeks to establish whether one week of treatment with Maraviroc, used at its approved dosage for HIV, is safe and tolerable in patients with SARS-CoV-2. | NCT04435522 | |
| Leronlimab (PRO 140) | CCR5 antagonist | 56 | Phase 2 | Active, not recruiting | The purpose of this study is to assess the safety and efficacy of Leronlimab administered as weekly subcutaneous injections in subjects experiencing prolonged symptoms (greater than12 weeks) of COVID-19. | NCT04678830 | |
| Reparixin | CXCR1/2 antagonist | 55 | Phase 2 | Terminated | To evaluate the efficacy and safety of Reparixin treatment as compared to the control arm in adult patients with severe COVID-19 pneumonia. | NCT04794803 | |
| Anti-platelet agents | |||||||
| Tirofiban | IIb/IIIa receptor inhibitor | 5 | Phase 2 | Completed | This study will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in COVID-19 patients. | NCT04368377 | |
| clopidogrel | P2Y12 antagonist | 750 | Phase 4 | Recruiting | This study will evaluate the efficacy of full-dose vs. standard prophylactic dose anticoagulation and of antiplatelet vs. no antiplatelet therapy for prevention of thrombosis in critically-ill COVID-19 patients. | NCT04409834 | |
| Ticagrelor | P2Y12 antagonist | 2000 | Phase 4 | Recruiting | This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic strategies for prevention of adverse outcomes in COVID-19 cases. | NCT04505774 | |
| Prasugrel | P2Y12 antagonist | 128 | Phase 3 | Not yet recruiting | The prevention of thrombogenic platelet activity with a P2Y12 inhibitor is superior to fixed dose enoxaparin alone. This treatment is feasible in all patients, regardless of the treatment regimen, except for specific contraindications. | NCT04445623 | |
| Aspirin | Cyclooxygenase Inhibition | 128 | Phase 3 | Enrolling by invitation | The early use of aspirin in COVID-19 patients, which has the effects of inhibiting virus replication, anti-platelet aggregation, anti-inflammatory and anti-lung injury, is expected to be beneficial. | NCT04365309 | |
| Dipyridamole | Inhibition of cAMP-phosphodiesterase | 100 | Phase 2 | Recruiting | Dipyridamole, which has anti-platelet and anti-inflammatory effects, may be useful in COVID-19 cases. | NCT04424901 | |
| TPO receptor agonists | |||||||
| EPAG | TPOR agonist | 120 | Phase 2 | Recruiting | A prospective, multicenter, randomized, open-label study to investigate the efficacy and safety of Eltrombopag plus rhTPO versus Eltrombopag as treatment for corticosteroid-resistant or relapsed ITP during the COVID-19 pandemic. | NCT04516837 | |
| Corticosteroids | |||||||
| Corticosteroid | Anti-inflammation | 86 | NA | Completed | This is a prospective randomized controlled trails to explore the effectiveness and safety of glucocorticoids in the treatment of novel coronavirus pneumonia. | NCT04273321 | |
| Corticosteroid | Anti-inflammation | 450 | Phase 4 | Recruiting | Timing of corticosteroids administration is very important in COVID-19 for the recovery and mortality decrease. | NCT04530409 | |
| Corticosteroid | Anti-inflammation | 184 | Phase 3 | Recruiting | Early use of corticosteroids, low dose, in mild disease, can decrease progression to respiratory failure and death. | NCT04451174 | |
| Dexamethasone | Anti-inflammation | 284 | Phase 3 | Recruiting | To randomly evaluate the efficacy and safety of the use of dexamethasone, a parenteral corticosteroid approved in Argentina, in patients COVID-19-induced ARDS. | NCT04395105 | |
| MP | Anti-inflammation | 173 | NA | Completed | A trial to analyze the association of low dose prolonged infusion of MP for patients with severe acute respiratory syndrome with composite primary end-point (ICU referral, need for intubation, in-hospital death at day 28). | NCT04323592 | |
| IVIG | |||||||
| IVIG | Immunomodulation | 76 | Phase 3 | Completed | To assess the efficacy of IVIG (medication trade name: Bioven) in the high immunomodulatory dose in complex treatment of severe pneumonia caused by SARS-CoV-2. | NCT04500067 | |
| IVIG | Immunomodulation | 50 | Phase 1/2 | Completed | To assess clinical efficacy and safety of single dose of Intravenously administered IVIG developed from convalescent plasma of recovered COVID-19 individual in severe and critically ill patients. | NCT04521309 | |
| IVIG | Immunomodulation | 10 | Phase 4 | Not yet recruiting | To evaluate the effect of IVIG on the hospital length of stay as well as production of inflammatory and non-inflammatory cytokines, biomarkers for endothelial injury, and biomarkers for coagulation via Mass Spectrometry. | NCT04616001 | |
| IVIG | Immunomodulation | 100 | Phase 2 | Completed | To determine if high dose intravenous IVIG plus SMT can reduce the proportion of participants dying or requiring ICU admission on or before day 29 or who are dependent on high flow oxygen devices or mechanical ventilation. | NCT04432324 | |
| Recombinant human ACE2 | |||||||
| RhACE2 APN01 | Neutralizing SARS-CoV-2 | 200 | Phase 2 | Completed | To evaluate the effect of rhACE2 as a treatment for patients with COVID-19 to block viral entry and decrease viral replication. | NCT04335136 | |
| rhACE2 | Neutralizing SARS-CoV-2 | ---- | NA | Withdrawn | This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients. | NCT04287686 | |
| ATR | Neutralizing SARS-CoV-2 | 1500 | Phase 4 | Recruiting | A pragmatic prospective, open-label, randomized controlled trial to examine the effectiveness of ARBs on improving the outcomes of people who tested positive for COVID-19. | NCT04394117 | |
| Anticoagulation therapy | |||||||
| Tinzaparin or Dalteparin | Anticoagulant | 166 | NA | Completed | To evaluate the efficacy of anticoagulation regime on the outcomes of critically ill patients via description of baseline characteristics and comorbidities before admission, and associate it with 28 days survival, survival outside ICU, thromboembolic event, and bleeding complications. | NCT04412304 | |
| Enoxaparin | Anticoagulant | 77 | Phase 2 | Terminated | A randomized open label trial to compare effectiveness of two dosing regimens currently used for prevention of clotting events in COVID-19 positive inpatients. | NCT0435927 | |
| Rivaroxaban | Anticoagulant | 400 | Phase 2 | Recruiting | Patients randomized into the rivaroxaban arm receive rivaroxaban OD until day 7 post randomization or hospital discharge, whichever occurs later, followed by a 28-day-phase of prophylactic anticoagulation. | NCT04416048 | |
| Heparin/ P2Y12 | Anticoagulant | 2000 | Phase 4 | Recruiting | A randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic strategies for prevention of adverse outcomes in COVID-19 positive inpatients | NCT04505774 | |
| Heparin sodium | Anticoagulant | 200 | Phase 4 | Recruiting | The combination of inhalation heparin combined with prophylactic doses of LMWH could reduce the progression to severe forms of the disease, and consequently the need for intensive care units and mechanical ventilation. | NCT04530578 | |
| Antithrombin | Anticoagulant | 48 | Phase 2 | Completed | A pilot clinical trial, single-center, exploratory, open, randomized, controlled, to study the efficacy and safety of human Antithrombin in patients with confirmed COVID-19 disease and criteria high risk to develop SARS. | NCT04745442 | |
| Antithrombin | Anticoagulant | 300 | NA | Recruiting | A multi-center, multinational, non-interventional, observational, retrospective, patient record study to assess changes in coagulation parameters in patients with severe COVID-19 receiving/not treatment with Antithrombin. | NCT04651400 | |
| TXA | Antifibrinolytic | 60 | Phase 2 | Not yet recruiting | A controlled trial of the drug TXA in inpatients recently admitted to the hospital with the diagnosis of COVID19. It is hypothesized that TXA will reduce the infectivity and virulence of the virus. | NCT04338126 | |
| TXA | Antifibrinolytic | 100 | Phase 2 | Not yet recruiting | A randomized, double-blind placebo controlled exploratory trial in order to determine whether TXA reduces infectivity and virulence of the SARS-CoV-2 virus. | NCT04550338 | |
| TXA | Antifibrinolytic | 100 | Phase 2 | Recruiting | A controlled trial of TXA in outpatients who were recently diagnosed with COVID-19. It is hypothesized that TXA will reduce the infectivity and virulence of the virus. | NCT04338074 | |
| Platelet transfusion | |||||||
| PRP | Increased platelets | 100 | NA | Recruiting | To evaluate the effect of PRP and cord blood in improving the symptoms of patients with COVID-19. | NCT04393415 | |
| aaPRP | Anti-inflammation | 30 | Phase 2 | Recruiting | To evaluate the potential of aaPRP and the outcomes for treating severe COVID-19 patients in ICU. | NCT04715360 | |
| Nebulized platelet lysate | Anti-inflammation; Immunomodulation | 1 | NA | Active, not recruiting | To evaluate and compare nebulized platelet lysate to placebo control of saline administered via handheld nebulizer 1X daily for eight weeks to determine its effect on lung function in patients with post-COVID-19 ARDS syndrome. | NCT04487691 | |
mAb: Monoclonal antibody; IL: Interleukin; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SOC: Standard-of-care; CRS: Cytokine release syndrome; MAS: Macrophage activation syndrome; CSS: Cytokine storm syndrome; TNFα: Tumor necrosis factorα; PK: Pharmacokinetics; PD: Pharmacodynamics; BSC: Best supportive care; CVC: Cenicriviroc; CCR: C-C chemokine receptor; HIV: Human immunodeficiency virus; CXCR: CXC chemokine receptor; EPAG: Eltrombopag; TPOR: Thrombopoietin receptor; rhTPO: Recombinant human thrombopoietin; ITP: Immune thrombocytopenia; ARDS: Acute respiratory distress syndrome; MP: Methylprednisolone; ICU: Intensive treatment unit; IVIG: Intravenous immunoglobulin; SMT: Standard medical treatment; ACE2: Angiotensin-converting enzyme; rhACE2: Recombinant human angiotensin-converting enzyme 2; ATR: Angiotensin receptor blockers; ARBs: Angiotensin II receptor blockers; OD: Once daily; LMWH: Low-molecular-weight heparin; TXA: Tranexamic acid; PRP: Platelet-rich plasma; aaPRP: Autologous activated platelet-rich plasma; No.: Number of patients; NA: Not available.