►Last Update: 3rd April 2020

Completed Trials

HCQ in Mild to Moderate COVID-19 Pneumonia

  • Parallel assignment blinded RCT (n = 62)

  • Single center, China

  • Admitted to general hospital ward with mild to moderate disease (P/F > 300) 

  • Groups

    • Arm 1: HCQ 200 mg BID x 5 days

    • Arm 2: Standard Care (including antiviral, systemic steroids). No placebo. 

  • Results

    • Improved time to clinical recovery (TTCR) by 1 day, defined as improvement in pulmonary symptoms (including objective cough frequency), resorption of pneumonic infiltrates on lung CT, and defervescence

    • Decreased risk of progression to severe illness 

  • Conclusions​: Provides stronger RCT evidence of the efficacy of HCQ in mild to moderate COVID-19, additive to antiviral therapy. 

Preliminary Report: Convalescent Plasma in Critically Ill COVID-19 Patients

  • High impact case series (n = 5)

  • Single center, China

  • All 5 subjects had severe ARDS on mechanical ventilation (2 - 11 days) and had been treated with systemic steroids and antivirals prior to plasma infusion 

  • Groups

    • Arm: Cross-matched convalescent plasma from COVID-19 survivors containing > 1:1000 total anti-SARS-CoV-2 IgG titre and > 1:40 neutralizing titre. 400 mL infused immediately after apheresis. 

  • Results

    • Improved oxygenation, defervescence, roughly 50% improvment in SOFA within 7 days

    • 3/5 liberated from vent and discharged within 2 weeks

    • Reduced viral load 

    • No comparator group, but outcomes better than historical controls

  • Conclusions​: Established a foundation for further controlled testing of convaslescent hyperimmune plasma for severe COVID-19

Azithromycin and HCQ for COVID-19 (Gautret Study)

  • Non-randomized pragmatic intervention trial (n = 36)

  • Multicenter, France

  • Groups

    • Arm 1: HCQ 600 mg QD x 10 days

    • Arm 2: Add on Azithromycin (Z-pak dosing) at clinician discretion to prevent bacterial superinfection

    • Arm 3: Nocebo

  • Results

    • HCQ + Azithromycin resulted in fastest rate of virological cure (clearance of nasopharyngeal viral load)​

    • No data on safety or adverse effects reported

  • Conclusions​

    • Reinforced the foundation for further testing of HCQ in a rigorous yet pragmatic RCT formal​

HC-nCOV: A Pilot Study of HCQ for "Common" COVID-19 Pneumonia 

  • RCT parallel assignment (n = 30)

  • Single center, China

  • Patients admitted to hospital with moderate COVID-19 disease 

  • Groups

    • Arm 1: HCQ 400 mg QD x 5 days

    • Arm 2: Placebo

  • Results

    • 1° Outcomes

      • No difference in illness severity

      • No difference in rate of virological clearance

      • No difference in rate of adverse events 

  • Conclusion: Negative but underpowered study, therefore inconclusive. Creates equipoise for rigorous RCT in a larger and potentially sicker patient population. 

Lopinavir-Ritonavir for Adults Hospitalized with Severe COVID-19

  • 1:1 RCT (n = 199)

  • Multisite, China

  • Patients were not critically ill. 75% required conventional oxygen NC therapy alone, and only 15% were enrolled from ICU. 

  • Groups

    • Arm 1: Lopinavir-Ritonavir (400-100 mg PO) BID x 14 days

    • Arm 2: Placebo

  • Results

    • 1° Outcomes

      • No change in 28-day all cause mortality

      • Median time to clinical improvement was 1 day shorter in Lopinavir-Ritonavir group

      • No change in virological cure 

  • Conclusion:

    • Lopinavir-Ritonavir is not beneficial in hospitalized patients who are not critically ill with COVID-19. Benefit may be seen in more severe illness. 

Recruiting Trials

CloroCOVID19: Chloroquine for SARS-COV-2 ARDS

  • Rationale: Chloroquine inhibits endosomal acification and interrupts trafficking of viral proteins

  • RCT parallel assignment (n = 440)

  • Multicenter, Phase 2, Brazil

  • Groups

    • Arm 1: Low dose CQ 450 mg BID x 5 days

    • Arm 2: High dose CQ 600 mg BID x 10 days

  • 1°: 28 day all-cause mortality 

  • Results: RECRUITING 

TOCIVID-19: Tocilizumab in COVID-19 Pneumonia (NCI Naples)

  • Rationale: IL-6 signaling plays a central role in COVID19-associated cytokine activation syndrome

  • Single group interventional trial (n = 330)

  • Multicenter, Phase 2, Italy

  • Groups

    • Arm 1: Tocilizumab 8 mg/kg IV q12 x 2 doses

    • Arm 2: Parallel observational cohort

  • 1°: 30 day all-cause mortality 

  • Results: RECRUITING 

Sarilumab in Hospitalized Patients with COVID-19 (Regeneron)

  • Rationale: IL-6 signaling plays a central role in COVID19-associated cytokine activation syndrome

  • Adaptive RCT parallel assignment (n = 400)

  • Multisite, Phase 2/3, New York

  • Groups

    • Arm 1: Sarilumab (low dose)

    • Arm 2: Sarilumab (high dose)

    • Arm 3: Placebo 

  • 1°: Time to clinical improvement 

  • Results: RECRUITING 

ACTT: Adaptive COVID-19 Treatment Trial (NIH/NIAID) of Remdesivir (RDV)

  • Rationale: RDV (GS-5734) is a broadly acting viral RNA polymerase inhibitor with promising antiviral activity against SARS-COV-2 in vitro

  • RCT parallel assignment (n = 440)

  • Multicenter, Phase 3, USA

  • Groups

    • Arm 1: RDV (200 mg day 1 + 100 mg days 2 - 10)

    • Arm 2: Placebo 

  • 1°: Clinical improvement (8-item ordinal scale)

  • Results: RECRUITING 

Remdesivir in Severe COVID-19 (Gilead) - Study A

  • RCT parallel assignment (n = 400)

  • Multicenter, Phase 3, USA

  • Groups

    • Arm 1: RDV IV (200 mg day 1 + 100 mg days 2-5)

    • Arm 2: RDV (200 mg day 1 + 100 mg days 2-10) 

  • 1°: Resolution of fever and hypoxemia 

  • Results: RECRUITING 

Remdesivir in Severe COVID-19 (Gilead) - Study B

  • RCT parallel assigment

  • Multicenter, Phase 3, USA

  • Groups:

    • Arm 1: RDV IV (200 mg day 1 + 100 mg days 2-5)

    • Arm 2: RDV (200 mg day 1 + 100 mg days 2-10) 

    • Arm 3: Placebo

  • 1°: Successful discharge at 14 days

  • Results: RECRUITING 

BEST-RCT: Bevacizumab in Critically Severe COVID-19

  • RCT parallel assigment

  • Multicenter, China and Italy

  • Groups:

    • Arm 1: Bevacizumab 7.5 mg/kg IV 

    • Arm 2: Placebo

  • 1°: Time to clinical improvement (ordinal scale)

  • Results: RECRUITING 

BARI-COVID: Baricitinib in COVID-19 (Prato)

  • JAK1/2 inhibitor 

  • Crossover trial, participants previously receiving an antiviral and/or HCQ

  • Single center, Italy

  • Groups:

    • Arm 1: Before crossover

    • Arm 2: Baricitinib 4 mg PO daily x 14 days

  • 1°: Percentage of patients requiring ICU 

  • Results: RECRUITING 

Efficacy and Safety of Corticosteroids in COVID-19

  • RCT

  • Multisite, China

  • Groups

    • Arm 1: Methylprednisolone 1 mg/kg daily x 7 days​

    • Arm 2: Placebo

  • 1°: Time to clinical deterioration

  • Results: RECRUITING 

Ascorbic Acid in COVID-19 (Palermo)

  • Single group intervnetional trial (n = 400)

  • Single center, Italy

  • Groups

    • Arm: Ascorbic acid, 10 gm IV

  • 1°: In-hospital mortality

  • Results: RECRUITING 

HCQ4-COV19: Treatment of Cases and Chemoprophylaxis of Contacts

  • Cluster RCT parallel assignment (n = 3040)

  • Single site, Phase 3, Wuhan

  • Groups

    • Arm 1: Low risk - rhIFN-alpha nasal drops QID​

    • Arm 2: High risk - rhIFN-alpha nasal drops QID + thymosin alpha-1 SQ x 1

  • 1°: Incidence of COVID-19 acquisition

  • Results: RECRUITING 

COVID19-PEP: Post-exposure Therapy for SARS-COV-2

  • RCT parallel assignment (n = 3040)

  • Single site, Phase 3, Minnesota (USA)

  • Groups

    • Arm 1: HCQ 1400 mg day 1 + 600 mg days 2-5

    • Arm 2: Placebo

  • 1°: Incidence of COVID-19 acquisition

  • Results: RECRUITING 

Recombinant IFN-alpha Nasal Drops for COVID-19 Prevention in HCWs

  • Parallel assignment interventional trial 

  • Multisite, Phase 3, Spain 

  • Prezcobix (Darunavir 800/Cobicistat 150) + HCQ x 7 days vs Placebo

  • 1°: Incidence of secondary COVID-19 cases

  • Results: RECRUITING 

Safety and Immunity of COVID-19 a-APC Vaccine

  • Single group interventional trial (n = 100)

  • Multisite, Phase 1, China

  • Groups

    • Arm: Ex vivo transduction of antigen presenting cells (APCs) with SARS-COV-2 structural genes​

  • 1°: Rate of positive T cell response

  • Results: RECRUITING 

Safety and Immunogenicity of COVID-19 mRNA Vaccine (NIH/NIAID)

  • Liposome encapsulate mRNA coding for SARS-COV-2 spike (S) protein

  • Single group interventional trial (n = 45)

  • Multisite, Phase 1, US (Emory and UW)

  • Groups

    • Arm 1: mRNA-1273 25 mcg IM (day 1 and 29)

    • Arm 2: mRNA-1273 100 mcg IM (day 1 and 29)

    • Arm 3: mRNA-1273 250 mcg IM (day 1 and 29)

  • 1°: Geometric fold increase in IgG from baseline 

  • Results: RECRUITING 

Information presented on this website does not reflect the views or positions of the US Veterans Health Administration, Emory Healthcare, or its affiliated institutions. This is a rapidly evolving field. As such. the content on this site is being updated daily and protocols will be updated in real time.  The purpose of this site is to provide a centralized resource for ICU topics and protocols to promote the well-being of hospitalized or critically ill patients suffering from COVID-19.  Defer to your institutional guidelines for all clinical practice decisions.

 

© 2020  Victor Tseng, MD