Corticosteroids for Post-Extubation Dysphagia (COPED)

Randomized Trial of Corticosteroids for Post-Extubation Aspiration

This is a placebo-controlled, double-blind randomized trial of a short course of intravenous corticosteroids for Acute Respiratory Failure Survivors with Fiberoptic Endoscopic Evaluation of Swallowing (FEES) documented laryngeal edema. Study was leveraged using the existing R01 grant infrastructure COMIRB # 21-3873, study design, and research methods. Patients for the study proposed will have already been enrolled in the R01 longitudinal cohort study. The sites to perform this study include Colorado, BU, Yale, Tufts, and Stanford. Those R01-enrolled patients with laryngeal edema on their initial FEES examination: defined as the revised Patterson edema score greater than zero, will be approached for enrollment.

Study Overview

• Status: Recruiting
• Conditions: Dysphagia; Laryngeal Edema
• Intervention / Treatment: Drug: Methylprednisolone; Drug: Normal Saline

Detailed Description

This is a multicenter study conducted across the University of Colorado, Boston University, Stanford University, Tufts Medical Center, and Yale University. The study aims to enroll a total of 80 participants, with approximately 20 participants at each site. This study aims to investigate the effects of intravenous corticosteroids on laryngeal edema and swallowing function in survivors of acute respiratory failure (ARF) who have documented laryngeal edema. It evaluates whether administering corticosteroids can reduce edema and improve quality of life related to swallowing after hospital discharge. The study includes ARF survivors with confirmed laryngeal edema, who will be randomized into two groups. Patients in the intervention group will receive 50 mg of methylprednisolone intravenously every six hours for a total of four doses, amounting to 200 mg (equivalent to 1,000 mg of hydrocortisone), while the control group will receive a saline placebo intravenously under the same regimen.

The primary outcomes of the study focus on measuring the reduction in laryngeal edema post-treatment and evaluating post-extubation swallowing function. Secondary outcomes include assessing quality of life one month after hospitalization, particularly regarding swallowing function and the ability to return to pre-hospitalization dietary habits. To measure laryngeal edema, the Revised Patterson Edema Scale will be utilized, which assesses edema across eight specific regions of the upper airway (such as the epiglottis and vallecula). Each area is rated on a scale from 0 to 3, resulting in an overall score ranging from 0 (normal) to 24 (severe edema). This scale has been adapted for the study to enhance sensitivity and reliability, showing moderate to good interrater reliability across assessed areas.

Participants will be randomized in a 1:1 ratio using a permuted block randomization method to ensure balanced allocation. The findings from this study could have significant implications for post-extubation care in ARF survivors, potentially guiding clinical practices for managing laryngeal edema and improving patients' swallowing function and overall quality of life after hospitalization.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna Matheson, BSN; Phone Number: 4848836222; Email: anna.matheson@cuanschutz.edu
• Study Contact Backup: Name: Jeffrey McKeehan, MSN; Phone Number: 3037246080; Email: jeffrey.mckeehan@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Principal Investigator: Marc Moss, MD
      • Contact: Jeffrey McKeehan, MSN; Phone Number: 3037246080; Email: jeffrey.mckeehan@cuanschutz.edu
      • Contact: Anna Matheson, BSN; Phone Number: 484-883-6222; Email: anna.matheson@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant enrolled in primary study COMIRB #21-3873/ NCT # 05108896
• Laryngeal edema identified on participants primary study Fiberoptic Endoscopic Evaluation of Swallowing (FEES) as defined as a revised Patterson edema score greater than zero
• Admission to an ICU during their hospitalization
• Mechanical ventilation with an endotracheal tube for greater than 48 hours.
• Extubation except for compassionate extubation or transition to end-of-life care.

Exclusion Criteria:

• Patient or provider refusal
• Contraindication or corticosteroids defined as an allergic reaction (extremely rate) or taking other immunosuppressive medications.
• Chronic treatment with corticosteroids (>= 40 mg Prednisone/day, >=32 Methylprednisolone/day)
• Contraindication to enteral/oral nutrition administration.
• Pre-existing history of dysphagia or aspiration.
• Pre-existing or acute primary central or peripheral neuromuscular disorder.
• Presence of a chronic tracheostomy (present prior to ICU admission).
• Pre-existing head and neck cancer or surgery.
• Coagulopathy resulting in uncontrolled nasal or pharyngeal bleeding.
• Delirium as assessed by CAM-ICU
• Inability to obtain informed consent from patient or an appropriate surrogate.
• Age <18 years.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Corticosteroid Intervention; 50 mg Methylprednisolone IV every 6 hours for 4 doses (total dose 200mg)	Drug: Methylprednisolone; 50 mg methylprednisolone IV every 6 hours for 4 doses to reduce laryngeal edema
Placebo Comparator: Placebo Control; Normal Saline placebo dose IV every 6 hours for 4 doses	Drug: Normal Saline; Normal Saline placebo IV every 6 hours for 4 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre/post intervention change in the revised Patterson edema scale on FEES exam	Investigators hypothesize that corticosteroids will be more effective (a larger pre/post reduction in the revised Patterson Edema scale) for resolution of swallowing dysfunction in patients recovering from acute respiratory failure with the presence of laryngeal edema on a FEES examination. Change is defined as the pre-study total FEES revised Patterson Edema scale minus the post-study total FEES revised Patterson Edema scale. Improvement in the total revised Patterson Edema scale would a positive number. For example, the pre-study total score was 15, the post-study total score was 8; therefore, the change would be a score of 7. Improvement in the total revised Patterson Edema scale would a positive number	Day 1 through Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Individual Components of the Revised Patterson Edema Scale	Since there is variability in the amount of edema in the eight different locations of the revised Patterson edema scale, investigators will examine the effect of corticosteroids compared to placebo on the change in edema in each of these eight areas. Change is defined as the pre-study FEES revised Patterson Edema scale minus the post-study FEES revised Patterson Edema scale. The scale assesses eight areas of the upper airway (epiglottis, vallecula, pharyngoepiglottic folds, aryepiglottic folds, arytenoids, false vocal cords, true vocal cords, and pyriform sinuses) using a normal, mild, moderate, or severe scale. For this proposal, we have adapted this rating system to a 0-3 scale (normal =0 and severe = 3) for each of the eight locations in the upper airway. The overall score can range from 0 (normal) to 24 (severe edema in all 8 areas). The overall interrater reliability of the revised Patterson scale maintains moderate-good agreement for each of the eight upper airway locations.	Day 1 through Day 5
Change in the Penetration-Aspiration Scale (PAS) Score	Investigators will determine whether the administration of corticosteroids results in improvement in the severity of dysphagia and aspiration. The PAS score is a validated measure of the degree of aspiration on FEES of the visualized swallowed bolus. A PAS score of 2-5 defined penetration of the bolus into the laryngeal area above the vocal cords but without entering the airway. A PAS score of 6 or greater defines as aspiration. A PAS score of 6-7 represents non-silent aspiration, and a score of 8 represents silent aspiration. Investigators will determine a PAS score for each bolus during the two FEES examinations.	Day 1 through Day 5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return to Pre-Hospitalization Diet	Participants will be contacted by telephone one month after hospital discharge to assess their return to Pre-Hospitalization Diet. A pre-hospitalization diet has already been established in the primary study, 21-3873. Study personnel will ask participants about their current diet post-discharge. Returning to the pre-hospitalization diet will be defined as resuming the same diet they followed before hospitalization.	1 month post-hospital discharge
Post-Discharge Eating Assessment Tool (EAT-10)	Participants will be contacted by telephone one month after hospital discharge to complete dysphagia screening tool to identify people at high risk of swallowing disorders. Each item corresponds to 5 difficulty levels from "no problem" to "serious problem," with a total score of 0 to 40. EAT-10 has good internal consistency and intraclass correlation coefficients (ICCs).	1 month post-hospital discharge
Post-Discharge Positive and Negative Affect Schedule (PANAS-SF)	Participants will be contacted by telephone one month after hospital discharge to complete 20-item questionnaire to assess positive affect (PA) and negative affect (NA). PA is associated with pleasurable engagement with the environment, whereas NA reflects a dimension of general distress summarizing a variety of negative states such as anger, guilt, or anxiety. Positive Affect Score: Add the scores on items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores can range from 10 - 50, with higher scores representing higher levels of positive affect. Mean Scores: 33.3 (SD±7.2) Negative Affect Score: Add the scores on items 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores can range from 10 - 50, with lower scores representing lower levels of negative affect. Mean Score: 17.4 (SD ± 6.2)	1 month post-hospital discharge
Post-Discharge Caregiver Assistance Scale (CAS)	Participants will be contacted by telephone one month after hospital discharge to complete an assessment tool to collect data on how much assistance the caregiver provides to the participant for various activities over the past month. A rating of zero (0) indicates "no" assistance is provided, while a rating of six (6) indicates "a lot" is provided.	1 month post-hospital discharge
Post-Discharge Caregiving Impact Scale (CIS)	Participants will be contacted by telephone one month after hospital discharge to complete an assessment tool to measure how much the participant's caregiver responsibilities interfere with different aspects of their life in their current living situation. Scoring ranges from zero (0), "Not at all" to six (6), "Very Much". If an item is not applicable, please circle zero (0) to indicate this.	1 month post-hospital discharge
Post-Discharge 20-Item Medical Outcomes Study (MOS) Social Support Survey	Participants will be contacted by telephone one month after hospital discharge to complete this survey to measure the availability of support for the participant in several domains. The survey comprises of 4 subscales and one overall summary index. The subscales include emotional/informational support, tangible support, affectionate support, and positive social interaction. The summary score is the overall social support. Scoring ranges from (1) "None of the time to" (6) "All of the time" for each domain.	1 month post-hospital discharge

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Marc Moss, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: September 19, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Otorhinolaryngologic Diseases; Pharyngeal Diseases; Laryngeal Diseases; Deglutition Disorders; Laryngeal Edema; Pharmaceutical Preparations; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pregnadienetriols; Prednisolone; Methylprednisolone; Saline Solution
• Other Study ID Numbers: 24-1535; R21AG089278 (U.S. NIH Grant/Contract)

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