Cromolyn Sodium for Treatment of COVID-19 Pneumonia

The study hypothesis is that cromolyn, when combined with standard COVID-19 treatment, will improve patient symptoms and reduce the number of days to improved quality of life.

Investigators will study the effects of adding cromolyn to the standard treatment of hospitalized patients with COVID-19 pneumonia and who require supplemental oxygen. Cromolyn will be administered as a nebulized treatment four times a day for four days followed by intranasal administration for two weeks. Investigators may also screen for biomarkers that could indicate inflammatory responses and treatment-induced improvement.

Participants will receive either study drug or placebo which will be administered by nebulization for 4 days followed by 14 days of intranasal administration. Participants will be followed while in the hospital and then as outpatients up to day 21 following randomization.

Study Overview

• Status: Terminated
• Conditions: Pneumonia, Viral; COVID-19 Pneumonia; COVID-19 Respiratory Infection
• Intervention / Treatment: Drug: Cromolyn Sodium; Other: Placebo

Detailed Description

The study will take place in two phases: Phase 1 will be an open label study of 10 patients who will all receive the Cromolyn nebulization treatment followed by Cromolyn nasal spray to assess tolerability and response to the study treatment. Investigators may also draw blood from 10 healthy patients who will be the controls for the cellular and cytokine assays. Phase 2 will be a randomized double blind placebo-controlled study of 50 patients randomized 1:1 to receive Cromolyn nebulization followed by Cromolyn intranasal spray vs. saline nebulization and saline intranasal spray.

While subjects are hospitalized, investigators will record morning pulse, respiratory rate and oxygen saturation. Morning and daily peak oxygen supplementation as indicated by the use of high flow nasal cannula, non-invasive ventilation, or invasive ventilation will be recorded. The investigators will also note any improvement or decline in participant's condition and any reduction or increase in oxygen supplementation.

Follow-up phone calls (or EMR review if still hospitalized) will be made on days 7, 14, and 21 to assess dyspnea and physical function. Validated questionnaires from the Patient-Reported Outcomes Measurement Information System (PROMIS) (https://www.healthmeasures.net/explore-measurement-systems/promis) will be used to evaluate dyspnea and physical function. Once discharged, patients will also be asked to maintain a daily log of nasal drug use, COVID-19 symptoms, resting pulse and oxygen saturation which will be reviewed at the 21 day virtual visit.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • EL Paso, Texas, United States, 79905
      • University Medical Center of El Paso

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. COVID-19 symptoms (fever, cough, sore throat, malaise, headache, muscle pain, dyspnea at rest or with exertion, confusion, or respiratory distress),
2. diagnosis of COVID-19 pneumonia with an admission chest x-ray demonstrating multilobar ground glass infiltrates consistent with COVID-19 pneumonia.
3. room air estimated PaO2/FiO2 ratio between 150 -280
4. must correct to a pulse oximetry of 90% or better using no more than 5 liters of low flow supplemental oxygen
5. must be enrolled within 24 hours of hospital admission

Exclusion Criteria:

1. immunocompromised due to current use of immunosuppressive drugs or chemotherapy, have a history of HIV/organ transplant/ active hepatitis B or C, or are on hemodialysis or peritoneal dialysis
2. currently on oxygen supplementation greater than low flow nasal cannula (including home oxygen therapy; CPAP for obstructive sleep apnea is not an exclusion)
3. have DNR status or not expected to survive >7 days
4. experiencing shock (on vasopressors) or multiple organ dysfunction or failure
5. are co-infected with influenza A or B
6. history of DVT or PE within last 12 weeks
7. currently pregnant or nursing
8. participating in another therapeutic trial
9. allergic to cromolyn sodium.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cromolyn; 2mL of 1% cromolyn sodium solution delivered via nebulizer 4 times a day for 4 days followed by 4% cromolyn solution administered intranasally 4 times per day for 14 days	Drug: Cromolyn Sodium; Nebulized treatment for 4 days followed by intranasal treatment starting on day 5.; Other Names: Nasal Crom
Placebo Comparator: Placebo; 2-3mL of normal saline delivered via nebulizer 4 times a day for 4 days followed by intranasal administration of normal saline 4 times per day for 14 days	Other: Placebo; Nebulized treatment for 4 days followed by intranasal treatment starting on day 5.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in requirement for oxygen supplementation based on daily assessment of flow (LPM or %Fi O2) and delivery device (cannula, mask, CPAP/BiPAP, ventilator)	Determination of trend in subject's need for oxygen supplementation over time.	up to 21 days
Change in respiratory symptoms (cough, shortness of breath, and fatigue) determined by data extraction from medical record, self-assessment by subject, or subject survey as appropriate for stage of the study.	Determination of trend in subject's respiratory symptoms over time.	up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hospital length of stay	number of days from admission to discharge	up to 21 days
change the patient score from the PROMIS survey provided to subjects at days 7, 14, and 21.	Determination of number of days to improved quality of life (QOL) from start of study treatment	up to 21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of return visits to hospital	any readmission to hospital after discharge	up to 21 days
assignment of COVID-19 outcomes	based on WHO classification	up to 21 days

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center, El Paso
• Investigators: Principal Investigator: Edward A Michelson, MD, Texas Tech University Health Sciences Center, Department of Emergency Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): May 23, 2024
• Study Completion (Actual): May 23, 2024

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19 pneumonia; Cromolyn sodium; Cromolyn
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Pneumonia; Respiratory Tract Infections; Pneumonia, Viral; Mast Cell Stabilizers; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Respiratory System Agents; Anti-Asthmatic Agents; Anti-Allergic Agents; Cromolyn Sodium
• Other Study ID Numbers: E21197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No