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

Trial Summary

What is the purpose of this trial?

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, 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.

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.

What data supports the effectiveness of the drug Methylprednisolone for swallowing difficulty?

Methylprednisolone has shown effectiveness in improving clinical conditions in patients with brain tumors and reducing inflammation in multiple sclerosis, suggesting its potential to help with conditions involving inflammation, which might be relevant for swallowing difficulties. ^{1 2 3 4 5}

Is methylprednisolone generally safe for humans?

Methylprednisolone, used under various names like Depo-Medrol and Medrol, has been associated with some safety concerns. There have been reports of serious side effects such as retinal toxicity and visual loss when injected improperly, and it has been linked to a condition called arachnoiditis in some cases. ^{3 4 6 7 8}

How is the drug Methylprednisolone unique for treating swallowing difficulty?

Methylprednisolone is a corticosteroid that reduces inflammation, which might help with swallowing difficulties by decreasing swelling in the throat. Its use in this context is unique because there are no standard treatments specifically for swallowing difficulties, making it a novel approach. ^{1 3 6 8 9}

Research Team

Marc Moss, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Methylprednisolone treatment in patients with brain tumors. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Absolute bioavailability of a new high dose methylprednisolone tablet formulation. [2013]

3. Australia pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. [2021]

4. Iran 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Retinal and choroidal microvascular embolism after intranasal corticosteroid injection. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. [2014]

9. United States pubmed.ncbi.nlm.nih.gov

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