Clinical trial NCT06686862: Non-Steroidal Anti-Inflammatory Drugs in Acute Myocarditis
Official title: Non-Steroidal Anti-Inflammatory Drugs Versus Conventional Treatment in Acute Myocarditis (INFLAMA Trial)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myocarditis Acute
Keywords: Nonsteroidal antiinflammatory agents
Magnetic Resonance Imaging
Lead sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sponsor class: OTHER
Collaborators: name: Fundación Investigación Biomédica Puerta de Hierro Majadahonda
First posted: 2024-11-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Prospective, randomized, multicenter, open-label clinical trial to evaluate the safety and efficacy of a 3-week ibuprofen tapering regimen compared to conventional analgesic treatment (acetaminophen) in patients with acute myocarditis and left ventricular ejection fraction ≥50%. The objective is to assess the reduction in late gadolinium enhancement on cardiac magnetic resonance imaging at 6-month follow-up.

Detailed description: The treatment for patients with uncomplicated myocarditis (left ventricular ejection fraction \>50% without heart failure) is not currently well defined. Analgesic drugs are commonly used to manage pain. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) among analgesics is controversial due to potential harmful effects observed in animal models. However, NSAIDs are the standard treatment for pericarditis, even when it is associated with mild myocardial involvement. In patients with acute myocarditis and normal left ventricular ejection fraction, observational studies have suggested that NSAIDs may have a beneficial effect in reducing late gadolinium enhancement (LGE) measured in cardiac magnetic resonance (CMR), an important prognostic marker in this population.

We plan to conduct a prospective, randomized, multicenter, open-label clinical trial to evaluate the safety and efficacy of NSAIDs versus conventional analgesic treatment in patients with uncomplicated acute myocarditis and left ventricular ejection fraction ≥50%.

Approximately 150 patients will be randomized 1:1 to NSAID treatment (ibuprofen tapering schedule during 3 weeks) or conventional treatment (acetaminophen or metamizole in case of allergy until pain resolution) during hospital admission. Patients will be followed for a 12-month period. Baseline CMR will be performed at initial hospitalization for acute myocarditis and at 3 and 6 months.

The primary objective is to assess the utility of ibuprofen versus conventional treatment with analgesics in acute myocarditis with preserved LVEF, in terms of reducing LGE on CMR at 6-month follow-up compared to baseline.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older.
* Patients hospitalized for confirmed acute myocarditis and left ventricular ejection fraction ventricular \>50%.
* Elevated troponin I/T (3 times above the upper limit of normal).
* Absence of acute heart failure.
* Absence of ischemic heart disease (ruled out by coronary angiography or coronary CT in individuals over 40 years).
* Diagnostic criteria for myocarditis (Lake Louise, 2018 update) by cardiac magnetic resonance imaging.

Exclusion Criteria:

* Kidney disease stage 3b, 4 and 5 (creatinine clearance by CKD-EPI \<45 ml/min/1.73 m2).
* Severe liver failure (Child-Pugh class C).
* Poorly controlled pharmacological hypertension (repeatedly systolic arterial pressure \>140 mmHg).
* Diagnosis criteria for acute pericarditis.
* Moderate or severe pericardial effusion (\>10 mm in total).
* Hypersensitivity to NSAIDs or previous use in the last 7 days.
* Contraindication for MRI.
* Participation in another clinical trial.
* Pregnancy, breastfeeding, or women of childbearing age unwilling to use appropriate contraception throughout the study.
* Any circumstance that, in the investigator's opinion, compromises participation in the clinical trial.

Primary outcomes:
measure: Change in late gadolinium enhancement (measured in % relative to indexed myocardial mass) compared to baseline (CMR) at admission)
timeFrame: 6 months
Secondary outcomes:
measure: Change in late gadolinium enhancement (measured in % relative to indexed myocardial mass by CMR) compared to baseline at 3 months.
timeFrame: 3 months
measure: Changes in T2 mapping values (measured in milliseconds by CMR) compared to baseline at 6 months.
timeFrame: 6 months
measure: Changes in T2 mapping values (measured in milliseconds by CMR) compared to baseline at 3 months.
timeFrame: 3 months
measure: Changes in T1 mapping values (measured in milliseconds) and extracellular volume (measured in %) by CMR compared to baseline at 6 months.
timeFrame: 6 months
measure: Changes in T1 mapping values (measured in milliseconds) and extracellular volume (measured in %) by CMR compared to baseline at 3 months.
timeFrame: 3 months
measure: Compare exercise capacity using METs (metabolic equivalent) in conventional treadmill exercise test at 3 months.
timeFrame: 3 months
measure: Proportion of patients experiencing arrhythmias during treadmill exercise test at 3 months
timeFrame: 3 months
measure: Proportion of patients from each group experiencing hospitalization due to recurrent myocarditis, heart failure, severe ventricular arrhythmias, or cardiovascular death at 12 months.
timeFrame: 1 year
measure: Proportion of patients developing adverse events in each treatment group at 1 month
timeFrame: 1 month
Other outcomes:
Locations:
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
state: Madrid
Study officials:
affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain
name: Fernando Domínguez-Rodriguez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain
name: Pablo García-Pavía, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: