Massachusetts General Hospital is participating in a number of local, regional and national clinical trials testing new therapies for COVID-19. Information about active trials will be posted here as it becomes available.

Immune Regulation

Efficacy of Tocilizumab on Patients With COVID-19

Responsible Party: John Stone, MD, MPH | Link to trial page

This is a randomized, double blind, multi-center study to evaluate the effects of tocilizumab compared to placebo on patient outcomes in participants with confirmed SARS-CoV-2 infection and evidence of systemic inflammation.

Data strongly suggest an immunologic link between COVID-19 and immune dysregulation resulting in MAS. We propose a trial of IL-6 receptor blockade with tocilizumab given early in disease course to try to prevent progression of COVID-19.

Participants will be randomized 2:1 to tocilizumab or placebo. Participants in the treatment arm will receive an intravenous (IV) injection of 8 mg/kg (not to exceed 800 mg) tocilizumab. Those in the control group will receive a placebo.

The primary outcome will be assessed by the proportion of patients who require mechanical ventilation, necessitating ICU admission.

Pegylated Interferon Lambda Treatment for COVID-19

Responsible party: Raymond Chung, MD | Link to trial page

Interferons are proteins produced by cells in the body that help to interfere with viral reproduction and direct the body’s immune response to infections.

Pegylated interferon-lambda is a lab-developed type III interferon made by Eiger BioPharmaceuticals that is currently being studied in clinical trials as a treatment for hepatitis D.

The objective of this study is to assess the efficacy of treatment with pegylated interferon lambda (180 mcg) vs. the standard of care among inpatient subjects with mild-to-moderate symptomatic COVID-19 and outpatient subjects with mildly symptomatic COVID-19.

The primary outcome measure will be a negative COVID PCR test seven days after treatment.

The trial is co-sponsored by Eiger BioPharmaceuticals.


Antivirals

Favipiravir

Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19

Site PI: Boris Juleg, MD, PhD | Link to trial page

This is an open label, randomized, controlled, multicenter Phase 2 proof-of-concept study of favipiravir in hospitalized subjects with COVID-19. Subjects will be randomized within their study site and stratified by the severity of their disease to receive either favipiravir + standard of care (SOC) or SOC alone.

The dose regimen will be 1800 mg favipiravir BID plus SOC or SOC alone on Day 1 followed by 1000 mg BID favipiravir (800 mg BID for subjects with Child-Pugh A liver impairment) plus SOC or SOC for the next 13 days. The primary outcome will be time to viral clearance.

Remdesivir

Adaptive COVID-19 Treatment Trial (ACTT)

Site PI: Elizabeth Hohmann, MD | Link to trial page

Remdesivir is an antiviral medication originally developed by the drug company Gilead as a potential treatment for the Ebola virus.

It works by inhibiting an enzyme called RNA polymerase that is used by many viruses to replicate. In previous lab studies, Remdesivir has proved effective in killing the SARS and MERS coronaviruses.

The Remdesivir trial is a double-blind, placebo-controlled trial where participants have a 50 percent chance of getting the treatment and 50 percent chance of receiving placebo. Mass General has enrolled approximately 30 patients in this trial as one of 54 recruiting sites.

  • Patients in the treatment group will receive 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir for the duration of the hospitalization—up to 10 days total.
  • Patients in the placebo group will receive 200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of placebo for the duration of the hospitalization up to 10 days total.

Outcomes will be determined by an eight-point clinical rating scale. The trial is sponsored by the National Institute of Health's National Institute of Allergy and Infectious Diseases, along with Gilead Pharmaceuticals.

Hydroxychloroquine

Outcomes Related to COVID-19 Treated with Hydroxychloroquine Among In-patients with Symptomatic Disease (ORCHID)

Responsible Party: Michael Filbin, MD | http://petalnet.org/studies/orchid (log in required)

The National Heart, Lung and Blood Institute (NHLBI) funded PETAL Network (http://petalnet.org/) recently launched the ORCHID trial—a multicenter blinded, placebo-controlled clinical trial evaluating hydroxychloroquine as a treatment for COVID-19 patients needing hospitalization. Mass General will be one of the enrolling sites under the direction of Michael Filbin, MD.

Hydroxychloroquine is an antimicrobial agent with immunomodulatory and antiviral properties that has demonstrated in vitro activity against the virus, but its effectiveness in COVID-19 is unknown and the drug has potential side effects.

Participants in the trial will be randomized to either five days of hydroxychloroquine treatment or placebo group:

  • Patients in the treatment arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next four days for a five-day total course.
  • Those in the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.

The primary outcome will be assessed at 15 days after treatment using a seven-point clinical rating scale.

The Clinical Coordinating Center for this trial is based at Mass General and is led by B. Taylor Thompson, MD, and David Schoenfeld, PhD. Vanderbilt University Medical Center is the lead clinical site with Wesley Self, MD, as the study's Principal Investigator.


Anticoagulants

Safety and Efficacy of Therapeutic Anticoagulation on Clinical Outcomes in Hospitalized Patients With COVID-19

Responsible Party: Mazen Albaghdadi, MD, MSc | Link to trial page

Given the established link between endothelial dysfunction and thrombosis in patients with cardiovascular disease, and the association between coagulopathy and adverse outcomes in patients with sepsis, the association between increased coagulation activity, end-organ injury, and mortality risk may represent a modifiable risk factor among COVID-19 patients with critical illness. Therefore, we propose to conduct a randomized, open-label trial of therapeutic anticoagulation in COVID-19 patients with an elevated D-dimer to evaluate the efficacy and safety.

After enrollment and blood collection, patients will then be randomized to therapeutic anticoagulation or standard of care anticoagulation. Both groups will receive heparin—those in the therapeutic group will receive a higher dose. Endpoints will be assessed through clinical outcomes.


Nitric Oxide

Nitric oxide (NO) gas works by widening blood vessels in the lungs that become constricted as a result of inflammation and formation of clots and can no longer provide the body with enough oxygen. The gas is frequently used as a first line treatment in premature babies and for oxygen-deprived newborn babies.

Preliminary data suggests that inhaled NO could have a virus-killing effect on SARS-CoV-2 due to the genomic similarities between this virus and those that caused the SARS and MERS outbreaks. Studies during the SARS outbreak in 2004-05 demonstrated that NO was effective in killing that virus.

Nitric Oxide Gas Inhalation in Severe Acute Respiratory Syndrome in COVID-19

Responsible Party: Lorenzo Berra, MD | Link to trial page

The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. Hypoxia is a condition in which the body cannot take in enough oxygen.

Intubated patients admitted to the intensive care unit with confirmed SARS-CoV-2 infection and severe hypoxemia will be randomized to receive inhalation of NO (treatment group) or not (control group).

The primary outcome will be change in arterial oxygenation at 48 hours from enrollment.

This study was conceived and sponsored by the Department of Anesthesia and the Respiratory Care Services at the Massachusetts General Hospital. Massachusetts General Hospital will also serve as a coordinating center for this international multicenter trial.

Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19

Responsible Party: Lorenzo Berra, MD | Link to trial page

The research team will assess inhaled nitric oxide as a treatment for patients with mild to moderate cases of COVID-19.

In COVID-19 patients who progress to more severe symptoms, the time period from symptom onset to development of dyspnea (difficult or labored breathing) is reported to be between 5 to 10 days, and then to severe respiratory distress syndrome from 10 to 14 days.

Preventing disease progression in spontaneously breathing patients with mild to moderate disease could help to reduce the number of severe cases and deaths, as well as lower the use of limited healthcare resources.

  • Patients in the treatment group will receive NO gas along with the standard of care for 30 minutes two times per day for 14 consecutive days
  • Patients in the control group will not receive the NO gas

The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19.

This study was conceived and sponsored by the Department of Anesthesia and the Respiratory Care Services at the Massachusetts General Hospital. Massachusetts General Hospital will also serve as a coordinating center for this international multicenter trial.

Inhaled Nitric Oxide (NO) Prevention of COVID-19 for HealthCare Providers

Responsible Party: Lorenzo Berra, MD | Clinical trial page

Thousands of healthcare workers have been infected with SARS-CoV-2 and contracted COVID-19 despite their best efforts to prevent contamination. No proven vaccine is available to protect healthcare workers against SARS-CoV-2.

This study will enroll 470 healthcare professionals dedicated to care for patients with proven SARS-CoV-2 infection. Subjects will be randomized either in the observational (control) group or in the inhaled nitric oxide group. All personnel will observe measures on strict precaution in accordance with WHO and the CDC regulations.

Individuals in the treatment group will be treated with 160 ppm of inhaled NO before and after their work shift and have daily monitoring of their body temperature or symptoms. The control group will not receive the inhaled NO but will have their body temperature and symptoms monitored daily as well. Participants in either group who have elevated temperatures or report symptoms will receive a test.

The primary outcome measure will be the percentage of subjects in each group with a positive test during the 14-day study period.


Treatment and Monitoring Strategies

Repeated Measures Trial of Temporary Automated Manual Ventilation Versus Noninvasive Oxygenation or Conventional Vent

Responsible Party: Keith Marill, MD | Link to trial page

The COVID-19 pandemic has led to a potential shortage of life-saving mechanical ventilators. The purpose of this study is to determine whether a novel simpler to device, the automated bag-valve-mask (BVM) compressor, can be used to provide assisted ventilation temporarily to patients in need. This includes patients with COVID-19 lung infection and respiratory failure. If successful, this would increase the pool of total available ventilator hours to alleviate any shortage.

All subjects will briefly be placed on the automated BVM compressor device. Measurements obtained while on this device will be compared to those obtained in the same subject prior to mechanical ventilation and while on a conventional ventilator.

The primary outcome will be arterial oxygenation obtained as measured by noninvasive pulse oximetry and arterial blood gas.

Non-Invasive Monitoring of Respiratory Function in Spontaneously Breathing Patients With COVID-19 Infection

Responsible Party: Omar Hyde, MD | Link to trial page

This study uses the AirGo band to monitor changes in tidal ventilation in spontaneously breathing patients with COVID-19 associated respiratory failure. It aims to recognize patterns of ventilation associated with worsening respiratory failure in this patient population.

If successful, this study will lead to the development of new robust methods for real-time, continuous monitoring of respiratory function in patients with respiratory failure. In turn, such monitoring methods may enable improvements in the medical management of respiratory failure and timing of interventions.