Corticosteroids for Swallowing Difficulty

(COPED Trial)

Overseen By Jeffrey McKeehan, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressives, Corticosteroids

Disqualifiers: Dysphagia, Neuromuscular disorder, Tracheostomy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 5 days

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a short course of corticosteroids, specifically methylprednisolone, can improve swallowing difficulties in survivors of acute respiratory failure. The researchers aim to determine if this treatment reduces throat swelling, a common issue after ventilator use. Participants will receive either the medication or a placebo to compare results. The trial seeks individuals who have been in the ICU, used a breathing machine for more than two days, and now experience throat swelling affecting swallowing. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on chronic corticosteroid treatment, you cannot participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that methylprednisolone, the treatment being tested, has been used effectively for various conditions. Research indicates that short-term use of methylprednisolone can help reduce swallowing problems after certain surgeries, suggesting it might benefit those with swallowing difficulties due to swelling in the voice box area.

However, like any medication, methylprednisolone can cause side effects. Some reported issues include swelling, skin rashes, and trouble breathing. These side effects are usually rare and depend on individual reactions.

Since this trial is in the early stages, there is some understanding of the treatment's safety, but more information is needed to confirm its tolerance for this specific use. Participants should discuss potential risks and benefits with the research team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for swallowing difficulty?

Researchers are excited about methylprednisolone for swallowing difficulties because it offers a new approach compared to current treatments, which often rely on rehabilitation therapies or dietary modifications. Unlike these options, methylprednisolone is a corticosteroid that potentially reduces inflammation in the throat, which can improve swallowing function more directly. Additionally, this treatment is administered intravenously, allowing for rapid action, which might provide quicker relief than traditional methods. This novel mechanism of targeting inflammation directly could be a game-changer for patients struggling with this condition.

What evidence suggests that this treatment might be an effective treatment for swallowing difficulty?

This trial will compare the effects of methylprednisolone with a placebo in addressing swallowing difficulties. Research has shown that methylprednisolone might help with these issues. In one study, 71.79% of patients who received steroids reported trouble swallowing after surgery, compared to 82.28% of those who did not receive steroids. Another study found that short-term use of methylprednisolone eased swallowing problems after certain surgeries. Methylprednisolone also reduces swelling in conditions like multiple sclerosis, suggesting it might help with swelling-related swallowing issues. Overall, these findings suggest that methylprednisolone could effectively reduce swallowing difficulties caused by swelling of the voice box. ^{4 5 6 7 8}

Who Is on the Research Team?

Marc Moss, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for Acute Respiratory Failure Survivors who have been previously enrolled in an R01 cohort study and show laryngeal edema on their initial FEES exam. It's not specified who can't join, but typically there would be criteria excluding certain patients.

Inclusion Criteria

I have been extubated for reasons other than end-of-life care.

Participant enrolled in primary study COMIRB #21-3873/ NCT #05108896

I was admitted to the ICU during my hospital stay.

Exclusion Criteria

I have a bleeding disorder causing uncontrolled nose or throat bleeding.

I have a history of swallowing difficulties or inhaling food/liquid into my lungs.

I cannot receive nutrition by mouth or feeding tube.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 50 mg of methylprednisolone intravenously every six hours for four doses or a saline placebo under the same regimen

5 days

Daily visits for 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of laryngeal edema and swallowing function

1 month

Telephone follow-up

Post-Discharge Assessment

Participants complete various assessments to evaluate quality of life, caregiver assistance, and social support one month after hospital discharge

1 month post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone

Trial Overview The trial tests if a short course of intravenous corticosteroids (Methylprednisolone) helps with swallowing difficulties post-extubation compared to a placebo (Normal Saline). The study is blinded, meaning neither the doctors nor the patients know who gets the real drug or placebo.

How Is the Trial Designed?

Group I: Corticosteroid Intervention Experimental Treatment 1 Intervention

50 mg Methylprednisolone IV every 6 hours for 4 doses (total dose 200mg)

Group II: Placebo Control Placebo Group 1 Intervention

Normal Saline placebo dose IV every 6 hours for 4 doses

Methylprednisolone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Two patients experienced vision loss in one eye after receiving a methylprednisolone acetate injection for chronic nasal inflammation, indicating a potential risk associated with this treatment.

The visual loss was linked to embolic occlusion of retinal and choroidal blood vessels, likely caused by microcrystal aggregates from the injected medication, highlighting a serious safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal and choroidal microvascular embolism after intranasal corticosteroid injection. Whiteman, DW., Rosen, DA., Pinkerton, RM.[2022]

The study found that the new high-dose (100 mg) methylprednisolone tablet has an absolute bioavailability of 82%, indicating it is effectively absorbed in the body when taken orally.

No adverse drug reactions were reported, and the tablet can safely substitute for intravenous methylprednisolone in high-dose therapy, as it produced expected changes in blood neutrophil counts without significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absolute bioavailability of a new high dose methylprednisolone tablet formulation. Groenewoud, G., Hundt, HK., Luus, HG., et al.[2013]

In a study of 15 patients previously diagnosed with corticosteroid-induced arachnoiditis, only 3 exhibited the clinical symptoms of arachnoiditis, suggesting a low incidence of the condition among those affected.

The findings indicate that the severity of radiological changes did not correlate with the severity of symptoms, leading to the conclusion that methylprednisolone acetate (Depo-Medrol) should be avoided in procedures involving the thecal sac due to potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. Johnson, A., Ryan, MD., Roche, J.[2021]

In a study of 10 patients with brain tumors, treatment with methylprednisolone sodium succinate (Solu-Medrol) led to significant clinical improvement and a reduction in periventricular elastance within 24 hours.

While periventricular elastance improved quickly, the reduction in intracranial pressure was not significant until the second day of therapy, indicating a delayed response for this particular measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylprednisolone treatment in patients with brain tumors. Miller, JD., Sakalas, R., Ward, JD., et al.[2019]

Inadvertent injection of methylprednisolone acetate into the eye during vitrectomy can lead to severe retinal toxicity, resulting in significant vision loss and complications such as retinal necrosis and optic nerve damage.

This case highlights the critical need for careful identification of medications during eye surgeries to prevent serious adverse effects associated with incorrect injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. Yonekawa, Y., Sun, G., D'Amico, DJ., et al.[2014]

A survey of sports medicine physicians revealed that 47% prescribe methylprednisolone taper (Medrol Dosepak) for sports injuries, particularly in patients aged 40 and younger, with postinjury disease being the most common reason for its use.

Concerns about complications, especially the risk of osteonecrosis (reported in 8.5% of prescribers), and a lack of proven efficacy were significant reasons for the 52% of physicians who chose not to prescribe Medrol Dosepak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. Langer, P., Fadale, P., Hulstyn, M., et al.[2018]

The study demonstrated that the test formulation of methylprednisolone produced in China is bioequivalent to the reference formulation (Medrol) from Pfizer, with pharmacokinetic parameters falling within the acceptable range for bioequivalence in both fasting and fed conditions.

No serious or unexpected adverse reactions were reported, indicating that both formulations were well tolerated by the 56 healthy subjects who completed the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions. Fan, L., Zhang, P., Gan, C., et al.[2023]

Methylprednisolone acetate (Depo-Medrol) injections via epidural or intrathecal routes can effectively relieve diskogenic back pain and radiculopathy when conservative treatments have failed, particularly if symptoms have lasted less than three months.

Corticosteroid injections are less effective for patients with chronic symptoms lasting over three months or those who have previously undergone surgery, suggesting a limited window for optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of diskogenic pain using epidural and intrathecal steroids. Brown, FW.[2019]

In a study of 901 patients with relapsing-remitting multiple sclerosis, methylprednisolone (MP) pulse therapy was administered with a mean frequency of 4 times, showing that the majority of patients received treatment multiple times, indicating its common use in managing acute exacerbations.

The study found that female patients were approximately 3.7 times more likely to seek MP pulse therapy compared to male patients, suggesting a gender difference in treatment-seeking behavior for MS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study related the incidence of methylprednisolone pulse therapy in patients visited multiple sclerosis clinic located at the isfahan kashani hospital. Tolou-Ghamari, Z., Shaygannejad, V., Ashtari, F.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5374993/

Effect of perioperative steroids on dysphagia after anterior ... Dysphagia or odynophagia reported 24-36h post-operatively in 56 (71.79%) steroid-treated patients compared to 130 (82.28%) control patients. ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03311425

Effect of Local Intraoperative Steroid on Dysphagia After ... The purpose of this study is to determine if the incidence and duration of postoperative dysphagia are improved in the participants receiving a local ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S152994301400566X

The clinical efficacy of short-term steroid treatment in ... Conclusions. The short-term use of systemic methylprednisolone after ACDF appears to be effective in relieving dysphagia and decreasing the PSTS.

4. thejns.org thejns.org/spine/view/journals/j-neurosurg-spine/29/1/article-p10.xml

Impact of local steroid application on dysphagia following an ... While the authors reported significantly lower rates of dysphagia in the immediate postoperative period as well as at the 1-month postoperative ...

5. withpower.com withpower.com/trial/phase-2-laryngeal-edema-10-2024-65be7

Corticosteroids for Swallowing Difficulty (COPED Trial) Methylprednisolone has shown effectiveness in improving clinical conditions in patients with brain tumors and reducing inflammation in multiple sclerosis, ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/methylprednisolone-injection-route/description/drg-20075216

Methylprednisolone (injection route) - Side effects & uses difficulty with swallowing; hives, itching, skin rash; puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue; trouble breathing ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12145300/

A Retrospective Review of Clinical Characteristics and ... We found that the use of prednisolone and IVIg were independent predictors of dysphagia. Systemic corticosteroid is typically used as the first line treatment ...

8. ijssurgery.com ijssurgery.com/content/11/2/9/tab-figures-data

Effect of perioperative steroids on dysphagia after anterior ... Dysphagia or odynophagia reported 24-36h post-operatively in 56 (71.79%) steroid-treated patients compared to 130 (82.28%) control patients. Perioperative ...