PCORI Biweekly COVID-19 Scan: Treatments for Patients With Acute Respiratory Distress Syndrome (March 18-31, 2021)

ECRI Horizon Scanning has selected the topics below as those with potential for impact relative to COVID-19 in the United States within the next 12 months. All views presented are preliminary and based on readily available information at the time of writing.

Because these topics are rapidly developing, we cannot guarantee the accuracy of this information after the date listed on this publication. In addition, all views expressed in the commentary section are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders. Topics are listed in alphabetical order.

Description

Lower respiratory tract infection by SARS-CoV-2 is associated with more severe cases of COVID-19. SNG001 (Synairgen plc, Southampton, United Kingdom) is an inhaled form of IFN-beta under development for treating patients hospitalized with COVID-19–related ARDS. IFN-beta is a cytokine with antiviral and immunomodulatory effects, responsible for promoting innate immune responses to viral infections. Viruses have evolved to evade host immune responses by suppressing natural IFN-beta production. SNG001 directly delivers IFN-beta to the lungs via nebulization to treat lower respiratory tract illnesses caused by COVID-19, while limiting systemic exposure to IFN-beta, which can cause flu-like symptoms.

A randomized, phase 2 trial of SNG001 in 101 patients hospitalized with COVID-19 found that patients receiving SNG001 for 14 days had greater odds of improvement on the World Health Organization’s Ordinal Scale for Clinical Improvement and were more likely to recover, defined as “no limitation of activities” or “no clinical or virological evidence of infection,” when compared with improvement and recovery in those receiving placebo. Treatment-related adverse events were more common in the SNG001 group than the placebo group (7 [15%] vs 2 [4%]). Cough occurred most frequently in the SNG001 group. SNG001 is under study in a randomized, placebo-controlled, phase 3 trial in 610 patients hospitalized with COVID-19–related ARDS, with primary completion expected in June 2021. ​

Commentary

SNG001 might improve patient health outcomes by helping the body’s antiviral response mitigate lower respiratory tract illnesses, which are associated with poor outcomes in people with COVID-19.

Early feedback from ECRI internal stakeholders suggested that SNG001 might be useful for treatment early in the COVID-19 disease course. Early results from the phase 2 trial suggest that SNG001 might improve clinical outcomes and assist in recovery from severe COVID-19. Thus, SNG001 might substantially impact burden on hospital resources when treating severe infections. Early treatment of COVID-19 might also help to protect patients from the sequela of more severe disease. However, SNG001 might cost more than other pharmaceutical interventions for hospitalized patients.

Stakeholders were concerned that, if expensive, SNG001’s use might increase disparities for individuals in need. The availability of other COVID-19 treatments and vaccines might limit the benefit of SNG001 to a small subset of people at high risk of COVID-19 respiratory complications.   

• Category: Treatments
• Areas of potential impact: Patient outcomes, health care delivery and process, health care disparities, health care costs 

Description

Pulmonary surfactant is a lipoprotein substance produced by the lungs. It prevents lung collapse, promotes oxygen exchange, and possesses antimicrobial activity. SARS-CoV-2 invades and damages type 2 alveolar cells, which produce pulmonary surfactant, impairing surfactant production in patients with COVID-19 and contributing to respiratory distress.

Pulmonary surfactant (animal-derived or synthetic) is approved by the FDA for use in premature infants with or at high risk of developing RDS, due to insufficient pulmonary surfactant production. The substance is administered in the trachea or bronchi in liquid form during endotracheal intubation or bronchoscopy.

Adults with non–COVID-19 ARDS treated with pulmonary surfactant have demonstrated a trend toward improved oxygenation but not improved death rates. However, COVID-19 ARDS displays atypical clinical signs, more similar to neonatal RDS than to adult non–COVID-19 ARDS. Pulmonary surfactant, therefore, might have better efficacy in adults with COVID-19 ARDS compared with non–COVID-19 ARDS.

Pulmonary surfactant to treat COVID-19 ARDS is in a phase 1/2 clinical trial in the United States, with primary completion expected in May 2021. Phase 2 trials are also ongoing in France and the United Kingdom. 

Based on available clinical trial dosing and pricing information we estimate that to treat COVID-19 ARDS in a 60-kg lean body mass adult costs $14 200 for a course of luminactant and between $12 600 and $23 800 for a course of poractant alfa. 

Commentary

Administering pulmonary surfactant is a novel approach to treating respiratory distress in COVID-19. Pulmonary surfactant has demonstrated safety and efficacy in neonatal RDS, which bears similarity to COVID-19 ARDS.

Early feedback from internal ECRI stakeholders suggested pulmonary surfactant is a promising treatment option for COVID-19 ARDS, given its success in treating neonatal RDS, with significant potential to improve patient outcomes. The magnitude of its impact likely hinges on how COVID-19 cases progress. It might not be as impactful if outpatient treatments and widespread vaccination reduce the number of patients hospitalized with respiratory failure. However, it represents an important treatment option for the patients who progress to respiratory failure in COVID-19.

Stakeholders expect that, as coronavirus variants emerge, the ongoing interest in developing treatments for serious infections might increase. Pulmonary surfactant is relatively costly, so it will need to demonstrate substantial efficacy in clinical trials to demonstrate cost savings.

• Category: Treatments
• Areas of potential impact: Patient outcomes, health care delivery and process, health care disparities, health care costs

Horizon scanning is a systematic process that serves as an early warning system to inform decision makers about possible future opportunities and threats. Health care horizon scanning identifies technologies, innovations, and trends with potential to cause future shifts or disruptions—positive or negative—in areas such as access to care, care delivery processes, care setting, costs of care, current treatment models or paradigms, health disparities, health care infrastructure, public health, and patient health outcomes.

The PCORI Health Care Horizon Scanning System (HCHSS) conducts horizon scanning to better inform its patient-centered outcomes research investments. Initially, PCORI defined the HCHSS project scope to focus on interventions with high potential for disruption in the United States in 5 priority areas: Alzheimer’s disease and other dementias, cancer, cardiovascular diseases, mental and behavioral health conditions, and rare diseases. In addition, the system captures high-level disruptive trends across all clinical areas, which may lead PCORI to expand the project scope to include other priority areas in the future.

In early 2020, the COVID-19 pandemic created a fast-moving, widespread public health crisis. In May 2020, PCORI expanded its HCHSS to elucidate the landscape of potentially impactful applications for COVID-19. The HCHSS COVID-19 supplement scans for, identifies, monitors, and reports on emerging and available COVID-19-related treatments, diagnostics, preventive measures, management strategies, and systems changes with potential for high impact to patient outcomes—for individuals and populations—in the United States in the next 12 months.

The HCHSS COVID-19 supplement produces 3 main outputs:

• Biweekly COVID-19 Scans (eg, this document) provide ECRI Horizon Scanning with a vehicle to inform PCORI and the public in a timely manner of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process.
• Status Reports (quarterly) briefly list and describe all COVID-19-related topics identified, monitored, and recently archived.
• High Impact Reports (every 4 months) highlight those topics that ECRI internal stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, and information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States.