Steroids for Myocarditis

(MYTHS Trial)

Recruiting at 59 trial locations

Overseen By Enrico Ammirati, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Niguarda Hospital

Must not be taking: Chronic corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disorders, Cancer ICIs, Infections, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 3

Duration: 3 days

288 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if giving high doses of a steroid medication can help patients with severe heart inflammation recover better. The treatment targets those with serious heart issues, aiming to reduce inflammation and improve heart function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic corticosteroid therapy or other chronic immunosuppressive therapies, you cannot participate in the trial.

What data supports the effectiveness of the drug Methylprednisolone for treating myocarditis?

Research shows that using steroids like prednisone, which is similar to Methylprednisolone, helped improve heart function and symptoms in children with myocarditis, with no significant side effects. Another study found that immunosuppressive therapy, including drugs like prednisolone, improved heart function and symptoms in patients with inflammatory myocarditis. ^{1 2 3 4 5}

Is methylprednisolone generally safe for humans?

Methylprednisolone has been used safely in many cases, but there are reports of side effects like heart rhythm problems and vision issues when used incorrectly. In a study on heart surgery, it helped reduce some complications without causing known drug-related problems. ^{6 7 8 9 10}

How does the drug methylprednisolone differ from other treatments for myocarditis?

Methylprednisolone is a corticosteroid that can be administered in high doses either orally or intravenously, which may offer flexibility in treatment compared to other options. Its ability to reduce inflammation by stabilizing cell membranes and decreasing immune response makes it unique, especially in conditions where inflammation is a key issue. ^{5 7 9 11 12}

Eligibility Criteria

Adults aged 18-69 with recent onset of cardiac symptoms, suspected acute myocarditis, heart failure signs, specific levels of NT-proBNP or BNP, reduced heart function on echocardiogram, and elevated troponin. Excludes those with autoimmune disorders, severe illness precluding treatment initiation, other trial participation, chronic corticosteroid/immunosuppressive therapy use, pregnancy, chronic infections like HIV/tuberculosis, out-of-hospital cardiac arrest history.

Inclusion Criteria

Randomization within 120 hours from hospital admission

I am between 18 and 69 years old.

My heart's pumping ability is reduced and its size is within normal limits.

Exclusion Criteria

I do not have an active bacterial or fungal infection.

I have an autoimmune disorder or a condition that benefits from immunosuppression.

The echocardiogram shows signs of other heart problems, like endocarditis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pulsed intravenous methylprednisolone or placebo for 3 days on top of standard therapy and maximal supportive care

3 days

Daily visits for 3 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary and secondary endpoints assessed over 6 months

6 months

Regular follow-up visits (in-person and virtual)

Data Lock and Analysis

Final data analysis and database lock after follow-up period

3 months

Treatment Details

Interventions

• Methylprednisolone

Trial Overview The MYTHS trial is testing the effectiveness of pulsed IV methylprednisolone (a steroid) against a saline solution placebo in patients with Acute Myocarditis. It's a phase III study where participants are randomly assigned to receive either the steroid treatment or placebo alongside standard care.

Participant Groups

Group I: Experimental arm Experimental Treatment 1 Intervention

Pulsed corticosteroid therapy (methylprednisolone 1 g IV qd for 3 days diluted in saline solution 250 mL) on top of standard therapy and maximal supportive care

Group II: Control arm Placebo Group 1 Intervention

Placebo (saline solution 250 mL IV qd for 3 days) on top of standard therapy and maximal supportive care.

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?

Niguarda Hospital

Lead Sponsor

Trials

76

Recruited

40,500+

Ministry of Health, Italy

Collaborator

Trials

63

Recruited

117,000+

Istituto Di Ricerche Farmacologiche Mario Negri

Collaborator

Trials

32

Recruited

74,800+

University of Milano Bicocca

Collaborator

Trials

153

Recruited

112,000+

Regione Lombardia

Collaborator

Trials

15

Recruited

54,100+

Findings from Research

In a study of 102 patients with dilated cardiomyopathy, those with active lymphocytic myocarditis (group I) showed a 60% improvement rate after treatment with immunosuppressive drugs, although 30% still died during the study.

Control biopsies indicated that 62% of patients treated with prednisone and azathioprine had a decrease in myocarditis, suggesting that while these drugs can help manage inflammation, they do not guarantee improved quality of life or increased survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lymphocytic myocarditis. Response to treatment with immunosuppressive drugs]. Arteaga-Fernánez, E., Barretto, AC., Mady, C., et al.[2013]

In a study of 68 children with acute myocarditis lasting 3 months, those treated with prednisolone showed a significant improvement in heart function, as measured by ejection fraction, compared to the control group after one month (p = 0.029).

By the end of the follow-up period, more children in the prednisolone group had an ejection fraction greater than 60%, indicating a notable recovery from left ventricular failure (p = 0.049).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute viral myocarditis: role of immunosuppression: a prospective randomised study. Aziz, KU., Patel, N., Sadullah, T., et al.[2021]

In a study of 16 patients with biopsy-proven myocarditis, immunosuppressive therapy (including azathioprine and prednisolone) led to significant clinical and hemodynamic improvements in most patients, with 12 out of 16 showing positive responses.

Despite the benefits, the therapy carries risks, as 4 patients deteriorated, with 2 fatalities occurring shortly after treatment initiation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive therapy in inflammatory myocarditis: long-term follow-up. Talwar, KK., Goswami, KC., Chopra, P., et al.[2019]

In a study of 13 children with biopsy-proven myocarditis, steroid therapy (prednisone) led to significant clinical improvements, including normalization of ECG changes and heart function, with no significant side effects reported.

Repeat biopsies showed improvement in all patients, with six out of eight showing elimination of inflammatory infiltrate, suggesting that immunosuppressive therapy can effectively enhance recovery in pediatric myocarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial. Chan, KY., Iwahara, M., Benson, LN., et al.[2021]

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]

A 41-year-old man developed atrial fibrillation after receiving oral methylprednisolone for membranoproliferative glomerulonephritis, highlighting a potential cardiac side effect of this medication.

While cardiac adverse effects are known with intravenous methylprednisolone, this case suggests that oral methylprednisolone may also pose similar risks, warranting further investigation into its cardiac safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrial fibrillation due to oral methylprednisolone in a patient with membranoproliferative glomerulonephritis. Dogukan, A., Ilkay, E., Poyrazoglu, OK., 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]

In a study of 150 patients undergoing coronary artery surgery, the use of methylprednisolone (Solu-Medrol) before cardiopulmonary bypass significantly reduced the incidence of myocardial infarction, cardiac arrhythmias, and pulmonary embolism compared to the control group.

The treatment with Solu-Medrol was associated with no serious complications, such as stress ulcers or infections, and even in patients with known duodenal ulcers, there were no post-operative bleeding incidents, suggesting its safety and efficacy in minimizing complications during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of methylprednisolone on the complications of coronary artery surgery. Rao, G., King, J., Ford, W., et al.[2019]

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]

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]

In a study involving eight elderly patients with rheumatoid arthritis, oral administration of methylprednisolone showed a relative bioavailability of 69.2%, indicating it is effectively absorbed when taken by mouth.

Both oral and intravenous (i.v.) routes of administration resulted in similar clinical responses, suggesting that oral methylprednisolone is a convenient alternative to i.v. therapy without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response. Hayball, PJ., Cosh, DG., Ahern, MJ., et al.[2019]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

[Lymphocytic myocarditis. Response to treatment with immunosuppressive drugs]. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Acute viral myocarditis: role of immunosuppression: a prospective randomised study. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Immunosuppressive therapy in inflammatory myocarditis: long-term follow-up. [2019]

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

Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial. [2021]

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

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

6. Czech Republic pubmed.ncbi.nlm.nih.gov

Atrial fibrillation due to oral methylprednisolone in a patient with membranoproliferative glomerulonephritis. [2019]

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

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

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

The effects of methylprednisolone on the complications of coronary artery surgery. [2019]

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

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

10. Australia pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. [2021]

11. 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]

12. Germany pubmed.ncbi.nlm.nih.gov

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response. [2019]