Non-Steroidal Anti-Inflammatory Drugs in Acute Myocarditis (INFLAMA)

Non-Steroidal Anti-Inflammatory Drugs Versus Conventional Treatment in Acute Myocarditis (INFLAMA Trial)

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.

Study Overview

• Status: Recruiting
• Conditions: Myocarditis Acute
• Intervention / Treatment: Drug: ibuprofen

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fernando Domínguez Rodríguez, MD, PhD; Phone Number: +34 91 1916000; Email: fdominguezr@salud.madrid.org

Study Locations

• Spain
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Puerta de Hierro-Majadahonda
      • Contact: Fernando Domínguez Rodríguez, MD, PhD; Phone Number: +34 91 1916000; Email: fdominguezr@salud.madrid.org
      • Contact: Noemí Ramos López; Email: nramosl@cnic.es
      • Principal Investigator: Fernando Domínguez-Rodriguez, MD, PhD
      • Principal Investigator: Pablo García-Pavía, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibuprofen; Ibuprofen tapering schedule during 3 weeks.	Drug: ibuprofen; Ibuprofen tapering schedule during 3 weeks. First week: Ibuprofen 600 mg every 8 hours. Second week: Ibuprofen 600 mg every 12 hours. Third week: Ibuprofen 600 mg every 24 hours.
No Intervention: Acetaminophen; Acetaminophen or metamizole in case of allergy until pain resolution, according to routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in late gadolinium enhancement (measured in % relative to indexed myocardial mass) compared to baseline (CMR) at admission)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in late gadolinium enhancement (measured in % relative to indexed myocardial mass by CMR) compared to baseline at 3 months.		3 months
Changes in T2 mapping values (measured in milliseconds by CMR) compared to baseline at 6 months.		6 months
Changes in T2 mapping values (measured in milliseconds by CMR) compared to baseline at 3 months.		3 months
Changes in T1 mapping values (measured in milliseconds) and extracellular volume (measured in %) by CMR compared to baseline at 6 months.		6 months
Changes in T1 mapping values (measured in milliseconds) and extracellular volume (measured in %) by CMR compared to baseline at 3 months.		3 months
Compare exercise capacity using METs (metabolic equivalent) in conventional treadmill exercise test at 3 months.		3 months
Proportion of patients experiencing arrhythmias during treadmill exercise test at 3 months		3 months
Proportion of patients from each group experiencing hospitalization due to recurrent myocarditis, heart failure, severe ventricular arrhythmias, or cardiovascular death at 12 months.		1 year
Proportion of patients developing adverse events in each treatment group at 1 month	Adverse events: severe adverse event, grade 3-4 adverse event, adverse reaction, special interest adverse event.	1 month

Collaborators and Investigators

• Sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Collaborators: Fundación Investigación Biomédica Puerta de Hierro Majadahonda
• Investigators: Principal Investigator: Fernando Domínguez-Rodriguez, MD, PhD, Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain; Principal Investigator: Pablo García-Pavía, MD, PhD, Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 12, 2024
• First Posted (Actual): November 13, 2024

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Nonsteroidal antiinflammatory agents
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Myocarditis; Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Phenylpropionates; Ibuprofen
• Other Study ID Numbers: 2024-513803-15-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Under agreement, individual or aggregated patient data could be shared with other scientific groups for scientific projects. Data can be shared only for scientific purposes and in full compliance with Personal Data Protection requirements in the EU.
• IPD Sharing Time Frame: After study scientific publication
• IPD Sharing Access Criteria: Under request to Study Chair
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No