Therapeutic Protocols for Hospitalized Patients

Current Priority Ranking for Enrolling Hospitalized Patients in COVID-19 Clinical Trials (JHED login required)

 

Study & PI
Summary
Feasibility of Targeting Driving Pressure for Lung Protective Ventilation in ARDs

PI: Sarina Sahetya
Lung protective ventilation is crucial to reduce mortality from acute respiratory distress syndrome (ARDs). Observational studies have suggested that Driving Pressure may be a more important target for lung protective ventilation when compared to plateau pressure. We propose to investigate the feasibility of a Driving Pressure-Guided ventilation strategy in a prospective cohort of ARDS patients.
The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2

PI: Ashwin Balagopal


This is a randomized, placebo-controlled, double-blinded clinical trial of the antiviral drug EIDD-2801 in hospitalized adults who present within seven days of symptom onset and within 48 hours of testing positive for SARS-CoV-2. EIDD-2801 is an orally bioavailable prodrug of a nucleotide analog designed to inhibit viral replication, which has shown antiviral activity in animal models of SARS-CoV- 1 and MERS.
A Phase 2/3 Single-Arm, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Remdesivir (GS-5734™) in Participants from Birth to 18 Years of Age with COVID-19

PI: Allison Agwu
In this study, eligible pediatric participants who are hospitalized with COVID-19 will be enrolled in 1 of 7 dosing cohorts based on weight and/or age and treated with remdesivir for up to 10 days to evaluate the safety, tolerability, pharmacokinetics and efficacy of remdesivir in participants under 18 years of age.
Safety and Pharmacokinetics of Human Convalescent Plasma in High Risk Children Exposed or Infected with SARS-CoV-2

PI: Sanjay Jain
Hospitalized and non-hospitalized children (1 month – <18 years) who are at high risk for disease progression and either have confirmed SARS-CoV-2 infection or a high-risk exposure are eligible for a single infusion of Human Coronavirus Immune Plasma.
COVID-19 Anticoagulation in Children – Thromboprophylaxis (COVAC-TP) Trial

PI: Anthony Sochet
This single-arm, open-label, non-randomized clinical trial evaluates the safety, dose-requirements, and exploratory efficacy of twice-daily subcutaneous enoxaparin as in-hospital venous thromboembolism (VTE) prophylaxis in children (birth to 18 years) hospitalized with signs and/or symptoms of COVID-19.
Prone Position and Respiratory Outcomes in Non-Intubated COVID Patients: The “PRONE” Study

PI: Mahendra Damarla
This is a randomized trial of prone vs. usual care positioning to determine if the improvements in oxygenation observed following prone positioning in mechanically ventilated patients with moderate-to-severe ARDS (induced by COVID-19 or otherwise) can also be achieved in spontaneously breathing, non-intubated, hospitalized COVID-19 patients.
Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial

PI: Franco D'Alessio
This double blind randomized placebo controlled study will test the hypothesis that the DNA methyltransferase inhibitor decitabine will augment the T cells known as Tregs, whose pro-repair function will help promote resolution of COVID-19 Acute Respiratory Distress Syndrome ( ARDS). Critically ill hospitalized adult participants who are diagnosed with COVID-19, meet acute respiratory distress syndrome (ARDS) criteria, and are receiving high flow oxygen or invasive/non-invasive mechanical ventilation will be randomized 1:1 to receive standard of care plus a single cycle of decitabine (10 mg/m2 daily for 5 days ) or standard of care plus placebo. The primary objective is to determine safety and efficacy of decitabine for COVID-19 ARDS based on clinical improvement within 10 days from the start of treatment, using a 6 point clinical scale.
Alpha-1 Adrenergic Receptor Antagonism to Prevent COVID-19 Cytokine Storm Syndrome and Acute Respiratory Distress Syndrome: A Randomized Study Comparing the Efficacy of Prazosin vs. Standard of Care for SARS-CoV-2 Infection

PI: Chetan Bettagowda

Prazosin, a pan-alpha-1 adrenergic receptor antagonist, will be investigated to assess its safety and efficacy in preventing COVID-19 cytokine storm and acute respiratory distress syndrome. Hospitalized adults who are between 45 and 85 years of age and do not require more than 4 liters/minute of supplemental oxygen by nasal cannula or ICU/CCU-level care at time of enrollment will be randomized 1:1 to receive oral prazosin for 28 days or standard of care. Treatment efficacy for preventing severe COVID-19 will be evaluated at day 60.
ARrest RESpiraTory Failure in Pneumonia (ARREST Pneumonia)

PI: Williams Checkley
The primary objective of this multi-center, double-blind, placebo controlled clinical trial is to establish the efficacy of early treatment with an inhaled corticosteroid (Budesonide) combined with a beta-agonist (Formoterol) vs. usual care for the prevention of acute respiratory failure in adults hospitalized with severe pneumonia, with confirmed or high-clinical suspicion for COVID-19 infection, and hypoxemia, who are not intubated prior to enrollment.
IMPAACT 2032 - Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the United States

PI: Sharon Nachman
This prospective, open label, non-randomized study will determine the pharmacokinetics of remdesivir and its metabolite GS-441524, as well as the clinical and laboratory safety outcomes (including infant outcomes), through 4 weeks after infusion and during delivery in pregnant women who are receiving remdesivir as part of their clinical care for the treatment of COVID-19. This information will be compared to the corresponding data obtained from non-pregnant women of childbearing potential who are also receiving this drug as part of their clinical care. Placental transfer of remdesivir will be assessed in plasma and cord blood samples collected at delivery from mothers who were dosed with this drug within the preceding 5 days.
A Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OP-101 (dendrimer n-acetyl-cysteine) in Patients with Severe COVID-19

PI: Nauder Faraday
Based on evidence from several preclinical models that OP-101 can target reactive macrophages and reduce proinflammatory cytokines and oxidative stress, this study will test the ability of OP-101 to reduce proinflammatory biomarkers (CRP, ferritin, and IL-6) and decrease time to improvement in clinical status for hospitalized participants with severe COVID-19. Eligible subjects must be enrolled within 72 hours from initiation of mechanical ventilation or high-flow oxygen and will be randomized to receive either a single IV infusion of OP-101 at the currently enrolling dose level, or placebo control, in a ratio of 3:1. All participants will receive standard of care treatment and will be followed for 30 days.
Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects with COVID-19 (FITE19)

PI: Errol Bush
The goal of this randomized, double-blind, placebo-controlled, multicenter study is to assess whether or not PTC299, an orally available inhibitor of dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine nucleotide synthesis, can treat COVID-19 in participants by arresting viral RNA replication and ultimately reducing the excessive cytokine release associated with severe disease. Eligible patients with COVID-19 who are hospitalized with confirmed pneumonia, but do not require mechanical ventilation, will be randomized 1:1 to a 14 day course of oral PTC299 treatment or placebo. Clinical benefit will be assessed by the time to respiratory improvement, beginning at randomization until discharge from the hospital or the end of the 28 -day study. All participants will also receive standard of care.
A Multi-center, Randomized, Sham controlled, Double-blind, Ascending-dose Study of Extracorporeal Mesenchymal Stromal Cell Therapy
(SBI-101 therapy) in COVID-19 Subjects with Acute Kidney Injury Receiving Renal Replacement Therapy

PI: Mohamed Atta
The primary objective of this study is to assess the safety and tolerability of a single treatment with the SBI-101 investigational cell therapy product to control the dysregulated inflammatory response in critically ill COVID-19 patients with acute kidney injury. Eligible subjects will also require either intermittent or continuous renal replacement therapy and may be mechanically ventilated. Initial participants will be enrolled into an open label, safety run-in, low dose cohort. Subsequently, a high dose cohort is planned to follow with some participants part of an open label safety group while another group will represent sham control subjects.
Novel Arm Restraint For Critically Ill Patients To Reduce Immobility, Sedation, Agitation and Cognitive Impairment

PI: Dale Needham


Closed to Enrollment

This ongoing study was recently amended to include COVID-19 patients. A within-patient, crossover, randomized controlled trial design is being used to evaluate a novel arm restraint device in adults age 50 and older who will require at least 2 days of treatment in the ICU to see if the device has beneficial effects such as reducing immobility, requirement for sedation and agitation. Patients, their family members and the clinical staff caring for these individuals will also be asked to provide feedback about their satisfaction with and acceptability/ perceptions of the device. This study was recently amended to include an a priori subgroup analysis comparing outcomes in non-COVID-19 versus COVID-19 patients.
Upward Incline Positioning in Hypoxemic COVID-19 Patients Prevents Development of Acute Respiratory Failure

PI: Luu Pham
Closed to Enrollment

The overall goal of this pilot study is to establish the feasibility of performing a randomized trial using a minimally invasive postural therapy approach to improve hypoxemia and reduce mechanical ventilation. Study aims include examining the acute effect of a 15-degree incline on hospital beds on oxyhemoglobin saturation, the feasibility of maintaining an inclined position, and the relative efficacy of positional therapy on measures of oxygenation and the need for mechanical ventilation over a 72-hour period. Eligible participants will have suspected or confirmed COVID-19 infection, and be enrolled within the first 24 hours after hospitalization for acute onset of symptoms defined as severe pneumonia requiring ≥ 2 L/min supplemental oxygen.
Convalescent Plasma to Limit Coronavirus associated Complications: A Randomized Blinded Phase 2 Study Comparing the Efficacy and Safety of Anti-SARS-COV-2 Plasma to Placebo in COVID-19 Hospitalized Patients (Contain COVID-19)

PI: Christian Merlo
Closed to Enrollment

This study will evaluate the efficacy and safety of convalescent plasma, which was obtained from donors who have recovered from COVID-19 and contains antibodies to SARS-CoV-2, in preventing worsening respiratory status or death in participants with COVID-19. Eligible participants must be within 3 days of presentation to the hospital with confirmed COVID-19 or within 3-7 days of symptom onset. Patients on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) are not eligible.
A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients with Life-Threatening COVID-19 Infection

PI: Nada Alachkar
Closed to Enrollment

This investigator initiated study will administer clazakizumab, a humanized IgG1 monoclonal antibody that binds to human IL-6, to COVID-19 patients in respiratory failure due to hyperinflammation resulting from a cytokine storm. Objectives include assessing efficacy by evaluating the incidence and duration of mechanical ventilation, the length of ICU stay and patient survival.
CRITICAL: CRIzanlizumab for Treating COVID-19 vAscuLopathy

PI: Charles Lowenstein
Closed to Enrollment

This randomized, double-blind, placebo-controlled trial aims to determine the therapeutic effect and tolerance of crizanlizumab in hospitalized patients with moderate stage coronavirus disease 2019 (COVID19). Crizanlizumab blocks P-selectin released by activated endothelial cells, thereby preventing leukocytes and platelets from adhering to the vessel wall, and limiting blockage and inflammation of small blood vessels. Outcomes will focus on biomarkers that indicate progression of disease.
A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination with Azithromycin in Patients with Moderate and Severe COVID- 19 Disease

PI: Richard Chaisson
Closed to Enrollment

The primary objective of this study is to test the efficacy of a 10 day course of hydroxychloroquine with or without a 5 day course of azithromycin in achieving a clinical response by day 15 in hospitalized adults with COVID-19 who are not critically ill (i.e. those who do not require ICU admission or mechanical ventilation).
A Phase 1 Double Blinded Randomized Placebo Safety and Early Efficacy Trial of Cord Blood Derived T-Regulatory Cell Infusions in the Treatment of COVID-19 Induced Acute Respiratory Distress Syndrome

PI: Douglas Gladstone
Closed to Enrollment

This study tests the hypothesis that infusing healthy, allogeneic T-regulatory (T-reg) cells to restore the normal inflammatory balance disrupted by COVID -19 may help resolve inflammation and improve the clinical outcomes in intubated patients suffering from moderate to severe acute respiratory distress syndrome (ARDS) secondary to COVID-19 infection. Cord Blood derived T-reg cells are given intravenously on days 0, 3, and 7, at one of two different doses versus placebo. Pre-existing medications are allowed as per the PI, as is some steroid use though high dose steroids (greater than 1mg/kg daily) are contraindicated.
A Phase 2, Open Label, Randomized Study of the Efficacy and Safety of Acalabrutinib with Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized with COVID-19

PI: Ephraim Fuchs

Closed to Enrollment

This randomized trial tests whether adding acalabrutinib to best supportive care (BSC; allows steroids or remdesivir) is safe and improves the outcome of hospitalized patients diagnosed with COVID-19. Hypoxemic but not critically ill inpatients will be randomized in a 1:1 ratio to receive acalabrutinib 100 mg po twice daily for 10 days plus BSC versus BSC alone. Acalabrutinib, a Bruton’s tyrosine kinase inhibitor, is hypothesized to work by binding to and inhibiting the NLRP3 inflammasome, a proximal mediator of the cytokine storm in COVID-19.
A Feasibility Study Assessing the Safety of Multiple Doses of Anti-SARS-CoV-2 Plasma in Mechanically Ventilated Intubated Patients with Respiratory Failure due to COVID-19

PI: David Hager
Closed to Enrollment

Recent observations suggest that passively administered antibodies from convalescent plasma has the potential to provide benefit against coronavirus infections. In this study, mechanically ventilated patients with respiratory failure due to COVID-19 will be administered multiple doses of convalescent plasma primarily to determine safety and feasibility, as well as secondarily to assess efficacy. All donors of convalescent plasma must meet the FDA’s current qualifications.
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants with COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

PI: David Hager
Closed to Enrollment

Ruxolitinib is a potent and selective inhibitor of JAK1 and JAK2. Participants will be randomized 2:2:1, ruxolitinib 5 mg BID: ruxolitinib 15 mg BID: placebo (placebo randomized 1:1 to match ruxolitinib 5 mg or 15 mg), to assess the efficacy and safety of 2 doses of ruxolitinib (5 mg and 15 mg BID) plus standard of care (SoC) therapy, compared with placebo plus SoC therapy. Subjects will be treated for 14 days with a possible extension to 28 days.
A Phase III Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS 181 for the Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects

PI: Shmuel Shoham
Closed to Enrollment

A sub-study to this ongoing protocol has been added that will investigate the potential clinical utility of DAS181, a viral receptor inactivator, in reducing viral burden and providing meaningful clinical benefit to patients infected with SARSCoV-2. It will primarily target COVID-19 patients who exhibit clinically significant impairment of respiratory function and may or may not be immunocompromised. This study is designed as a two stage randomized (1:1), placebo-controlled, double-blind trial.
A Multi-center, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

PI: Noreen Hynes
Closed to Enrollment

The current protocol will evaluate the combination of the Janus Kinase inhibitor baricitinib and the anti-viral drug remdesivir compared to remdesivir alone for the treatment of hospitalized subjects with COVID-19. This change was made following a preliminary review of data from the first stage of this study, ACTT-1, which showed better clinical outcomes for subjects who received remdesivir compared to placebo.