The Effects of Hydroxychloroquine in Patients with Inflammatory Cardiomyopathy

Official title

The Efficacy and Mechanism of Hydroxychloroquine in Patients with Inflammatory Cardiomyopathy After Myocarditis

Overview

Evaluating the long-term therapeutic effects and safety of hydroxychloroquine(compared to glucocorticoid therapy alone) in patients with inflammatory cardiomyopathy--a multicenter randomized controlled study

Detailed description

Inflammatory cardiomyopathy is the chronic stage of myocarditis, which is associated with poor cardiovascular outcome and poor prognosis.Inflammatory cardiomyopathy is also one of the common causes of heart failure. Actually, the treatment and prognosis of inflammatory cardiomyopathy remain challenging clinical issues that often have frustrating consequences. So far, there is no specific treatment for inflammatory cardiomyopathy. Hydroxychloroquine is a drug that can effectively inhibit inflammation and has been used in many inflammatory diseases in the past. Our previous basic research has proved that hydroxychloroquine can effectively treat experimental autoimmune myocarditis.Therefore, multicenter large randomized controlled trials are needed to verify the therapeutic effects of hydroxychloroquine on patients with inflammatory cardiomyopathy.

Patients with inflammatory cardiomyopathy after acute myocarditis confirmed by biopsy received standard drug treatment for heart failure. These patients whose cardiac function could not be improved for a long time were randomly assigned (1:1) to hydroxychloroquine group (hydroxychloroquine and glucocorticoid) and glucocorticoid group (glucocorticoid alone). The clinical benefit will be measured with respect to absolute increase in LVEF and decrease in hs-cTnI and NT-proBNP of immunosuppressive treatment with hydroxychloroquine and prednisolone compared to prednisolone alone at long-term follow-up (1, 3, 6, 9, 12, 18, 24, 36 months).

Interventions

• Drug Hydroxychloroquine
  Hydroxychloroquine 200mg qd
• Drug Prednisolone
  Prednisolone 20mg qd

Primary outcome measures

• Composite cardiovascular outcome [Time frame: 3 years]

Secondary outcome measures (6)

• The increase and dynamic changes of LVEF (%) [Time frame: 3 years]
• The increase and dynamic changes of LVIDd (mm) [Time frame: 3 years]
• The decrease and dynamic changes of hs-cTnI (pg/mL) [Time frame: 3 years]
• The decrease and dynamic changes of NT-proBNP (pg/mL) [Time frame: 3 years]
• The decrease and dynamic changes of hs-CRP (mg/L) [Time frame: 3 years]
• The decrease and dynamic changes of ESR (mm/H) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Male or female patient aged from 18 to 80 years;
• Left ventricular dysfunction \[left ventricular ejection fraction (LVEF) <50%\] diagnosed by echocardiography (Simpson's biplane) within 30 days before randomization;
• Chronic heart failure (lasting >6 months) unresponsive to conventional supportive therapy;
• High-sensitivity cardiac Troponin I (hs-cTnI) >26.2 pg/mL and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) >169pg/mL;
• Suffered from confirmed fulminant myocarditis in the past;
• Diagnosed with chronic inflammatory cardiomyopathy confirmed by myocardial biopsy1;
• Absence of cardiotropic viruses at polymerase chain reaction analysis;
• Volunteer for the study and written informed consent;

Exclusion criteria

• Age <18 or >80 years;
• Acute myocardial infarction occurred within the past month;
• Subjects who have undergone cardiac surgery or cerebrovascular accidents within 6 months;
• Preparing for heart transplantation;
• With malignant arrhythmias such as long QT syndrome;
• Pregnancy or lactation;
• Have participated in any drug clinical trial within the three months;
• Presence of contraindications to prednisolone and/or hydroxychloroquine (including hypersensitivity to prednisone or hydroxychloroquine, mainly untreated systemic infection, uncontrolled diabetes, poorly controlled endocrine diseases, osteoporosis, gastric or duodenal ulcer, uncontrolled hypertension, leukocytopenia (leukocyte counts < 4×109/L), neutropenia (neutrophils < 1.5×109/L), thrombocytopenia (platelet levels < 130×109/L), anemia (hemoglobin levels < 11 g/dL).
• Confirmed or possible systemic inflammatory diseases;
• On the brink of death or life expectancy of less than 1 year;
• Drug or alcohol abuse;
• cannot persist in taking medication due to various reasons;
• Inability to provide informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Hospital — Wuhan

Publications

• He W, Zhou L, Xu K, Li H, Wang JJ, Chen C, Wang D. Immunopathogenesis and immunomodulatory therapy for myocarditis. Sci China Life Sci. 2023 Sep;66(9):2112-2137. doi: 10.1007/s11427-022-2273-3. Epub 2023 Mar 29. PMID 37002488
• Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, Friedrich MG, Klingel K, Lehtonen J, Moslehi JJ, Pedrotti P, Rimoldi OE, Schultheiss HP, Tschope C, Cooper LT Jr, Camici PG. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ Heart Fail. 2020 Nov;13(11):e007405. doi: 10.1161/CIRCHEARTFAILURE.120.007405. Epub 2020 Nov 12. PMID 33176455
• Hang W, Chen C, Seubert JM, Wang DW. Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes. Signal Transduct Target Ther. 2020 Dec 11;5(1):287. doi: 10.1038/s41392-020-00360-y. PMID 33303763
• He W, Cui G, Chen J, Chen M, Li R, Wang L, Yu T, Li G, Jiang J, Wang DW. The efficacy and safety of hydroxychloroquine in patients with chronic inflammatory cardiomyopathy: a multicenter randomized study (HYPIC trial). BMC Med. 2025 Aug 8;23(1):467. doi: 10.1186/s12916-025-04301-w. PMID 40781621

Identifiers

NCT: NCT05961202 · TJ-HYPIC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗