Back to resultsHydroxychloroquine in Colchicine-Resistant Glucocorticoid-Dependent Idiopathic Recurrent Pericarditis (RESTORE)
Primary Purpose
Pericarditis Idiopathic Recurrent
Status
Not yet recruiting
Phase
Phase 3
Locations
Greece
Study Type
Interventional
Intervention
Hydroxychloroquine
Colchicine
Sponsored by
About this trial
This is an interventional prevention trial for Pericarditis Idiopathic Recurrent
Eligibility Criteria
Inclusion Criteria: Male or female patients aged≥18 years Idiopathic recurrent pericarditis with at least 2 recurrences Recurrent pericarditis defined as a first episode of acute pericarditis followed by recurrences (at least two recurrences for this study). First episode of pericarditis is diagnosed when at least two of the following criteria were present: pericarditis typical chest pain (sharp and pleuritic, improved by sitting up and leaning forward), pericardial friction rubs, widespread ST segment elevation or PR interval (PR) depressions not previously reported, and new or worsening pericardial effusion. Recurrence is diagnosed when chest pain recurs and one or more of the following signs is present: fever, pericardial friction rub, ECG changes, echocardiographic evidence of new or worsening pericardial effusion, and elevations in the white blood cell count, erythrocyte sedimentation rate or C-reactive protein. To be enrolled in this study, elevation of C-reactive protein is mandatory both in the first attack and in the following recurrences. The investigators differentiate recurrences from incessant pericarditis, term used to define patients with continued activity of pericarditis (with a symptom-free interval of < 6 weeks) Specific aetiologies excluded, including tuberculous, neoplastic or purulent aetiologies, post-cardiac injury syndromes, and rheumatic autoimmune diseases. Female subjects must be postmenopausal, or incapable of pregnancy or permanently sterile, or if of childbearing potential must agree to use highly-effective method of contraception. Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule. Exclusion Criteria: Ophthalmologic contraindications Structural heart disease Corrected QT interval >440msec in men and >450msec in women Left ventricular hypertrophy >13mm in men and >11mm in woman Known allergy or intolerance to hydroxychloroquine Life expectancy of < 12 months Complex congenital heart disease History of ventricular arrhythmias other than isolated extrasystoles Women who are pregnant (as evidenced by pregnancy test if pre-menopausal) Known channelopathy such as Brugada syndrome, long QT syndrome, or Catecholaminergic monomorphic ventricular tachycardia On the heart transplant list
Sites / Locations
- "Hippokration" General Hospital of Athens
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Hydroxychloroquine arm
Colchicine arm
Arm Description
Hydroxychloroquine 400mg daily
Colchicine continued
Outcomes
Primary Outcome Measures
Recurrence Rate
The diagnosis of RP in a patient with history of a documented episode of acute pericarditis according to ESC guidelines was established in the presence of at least 2 of the following conditions: i. pleuritic chest pain, ii. pericardial friction rub, iii. ECG compatible with acute pericarditis and iv. first detected or increasing in size pericardial effusion. C-reactive protein (CRP) elevation was considered a confirmatory finding. Since RP frequently underlines a secondary etiology, an extensive work-up was performed to exclude such diseases. In particular, apart from the first line evaluation, second level investigations were additionally performed such as thyroid function tests, chest and abdominal computed tomography, serological screening for autoimmune disorders, serum tumor markers and QuantiFERON-Tuberculosis Gold test.
Secondary Outcome Measures
Time to Pericarditis Recurrence
Time to pericarditis recurrence (from randomization to 1st recurrence). Kaplan-Meier. Clinical Events Committee (CEC)-confirmed recurrences used for primary analysis.
Dose of the Corticosteroid in the time of the recurrence
State-Trait Anxiety Inventory (STAI)
This score measures two types of anxiety- state anxiety (S-anxiety) and trait anxiety (T-anxiety). It includes 40 self-reported items on a 4-point Likert scale. The scores range from 20 to 80, with higher scores correlating with greater anxiety. The 4-point scale for S-anxiety is as follows: 1) not at all, 2) somewhat, 3.) moderately so, 4) very much so. The 4-point scale for T-anxiety is as follows: 1) almost never, 2) sometimes, 3) often, 4) almost always.
Change over time of pericardial pain
Quantified using the four-point pain verbal rating scale (VRS-4). Minimum: 0, maximum: 3). Higher score indicates worse outcomes.
Change over time of C-reactive protein levels
Measured in mg/dL
Change over time of echocardiographic effusion
Measured in ml
Incidence and severity of Adverse Events
All adverse events (AEs) will be monitored and recorded to assess the tolerability and safety of the treatment.
Full Information
NCT ID
NCT05737680
First Posted
January 30, 2023
Last Updated
February 20, 2023
Sponsor
Hippocration General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05737680
Brief Title
Hydroxychloroquine in Colchicine-Resistant Glucocorticoid-Dependent Idiopathic Recurrent Pericarditis
Acronym
RESTORE
Official Title
Efficacy and Safety of Hydroxychloroquine in Colchicine-RESistant Glucocorticoid-DependenT IdiOpathic REcurrent Pericarditis: A Randomized Clinical Trial (The RESTORE Randomized Clinical Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 2023 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hippocration General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Among patients with colchicine-resistant glucocorticoid-dependent idiopathic RP (idiopathic recurrent pericarditis during at least a second recurrence, having met the 2015 European Society of Cardiology criteria for pericarditis at least once), HCQ 400mg daily is associated with a reduce the risk of recurrence.
The above hypothesis will be tested with a randomized, prospective, parallel, open label clinical trial. The expected study duration is approximately 12 months from the time the first subject is enrolled (planned for February 2023) to the time of study's termination date (December 2024). The researchers will obtain approval by the institutional review board (IRB).
Detailed Description
Recurrent pericarditis (RP) along with pericardial tamponade and constrictive pericarditis are potential complications of acute pericarditis. They appear most frequently in secondary forms of pericarditis as compared with idiopathic acute pericarditis. Among the above-mentioned complications, RP is a highly problematic and disabling condition, which severely impairs the quality of life of affected patients, since it often requires emergency department visits and hospitalizations.
Moreover, the side effects of treatment constitute an additional concern both for the managing physicians and affected patients. In the most recent guidelines for the diagnosis and management of pericardial diseases of the European Society of Cardiology (ESC), a stepwise approach has been proposed for the treatment of RP including 4 treatment lines according to disease severity and individual response to treatment. Among them hydroxychloroquine (HCQ), an anti-malarial drug with immunomodulatory properties could potentially have a role as a third step treatment. HCQ, is an established treatment for all patients with systemic lupus erythematosus (SLE) including those with serositis (pericarditis, pleuritis) but data on HCQ efficacy for refractory idiopathic RP (IRP) are very scant.
The potential Anti-interleukin-1 agents are characterized by some disadvantages such as a long duration of therapy as well as high costs. In addition to this, only patients with a clear inflammatory pattern are candidates. Patients with mild or doubtful symptoms and/or normal or near normal levels of C-Reactive protein are not good candidates for anti-IL-1 therapy.
The investigators propose a randomized, prospective, parallel, open label, clinical trial, which will provide data on the efficacy and safety of HCQ in colchicine-resistant glucocorticoid-dependent idiopathic RP. The trial will have two study arms: HCQ 400mg daily vs. Colchicine continued. Patients with RP (idiopathic recurrent pericarditis during at least a second recurrence, having met the 2015 European Society of Cardiology criteria for pericarditis at least once) will be randomized to HCQ vs. Colchicine and will receive optimal post-recurrence care (increase the dose of methylprednisolone by 8 mg and then decrease by 2 mg every 2 weeks) in both arms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pericarditis Idiopathic Recurrent
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Hydroxychloroquine arm
Arm Type
Active Comparator
Arm Description
Hydroxychloroquine 400mg daily
Arm Title
Colchicine arm
Arm Type
Active Comparator
Arm Description
Colchicine continued
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine 400mg daily
Intervention Type
Drug
Intervention Name(s)
Colchicine
Intervention Description
Colchicine continued
Primary Outcome Measure Information:
Title
Recurrence Rate
Description
The diagnosis of RP in a patient with history of a documented episode of acute pericarditis according to ESC guidelines was established in the presence of at least 2 of the following conditions: i. pleuritic chest pain, ii. pericardial friction rub, iii. ECG compatible with acute pericarditis and iv. first detected or increasing in size pericardial effusion. C-reactive protein (CRP) elevation was considered a confirmatory finding. Since RP frequently underlines a secondary etiology, an extensive work-up was performed to exclude such diseases. In particular, apart from the first line evaluation, second level investigations were additionally performed such as thyroid function tests, chest and abdominal computed tomography, serological screening for autoimmune disorders, serum tumor markers and QuantiFERON-Tuberculosis Gold test.
Time Frame
12 months follow-up
Secondary Outcome Measure Information:
Title
Time to Pericarditis Recurrence
Description
Time to pericarditis recurrence (from randomization to 1st recurrence). Kaplan-Meier. Clinical Events Committee (CEC)-confirmed recurrences used for primary analysis.
Time Frame
12 months follow-up
Title
Dose of the Corticosteroid in the time of the recurrence
Time Frame
12 months follow-up
Title
State-Trait Anxiety Inventory (STAI)
Description
This score measures two types of anxiety- state anxiety (S-anxiety) and trait anxiety (T-anxiety). It includes 40 self-reported items on a 4-point Likert scale. The scores range from 20 to 80, with higher scores correlating with greater anxiety. The 4-point scale for S-anxiety is as follows: 1) not at all, 2) somewhat, 3.) moderately so, 4) very much so. The 4-point scale for T-anxiety is as follows: 1) almost never, 2) sometimes, 3) often, 4) almost always.
Time Frame
3,6,9,12 months follow-up
Title
Change over time of pericardial pain
Description
Quantified using the four-point pain verbal rating scale (VRS-4). Minimum: 0, maximum: 3). Higher score indicates worse outcomes.
Time Frame
3,6,9,12 months follow-up
Title
Change over time of C-reactive protein levels
Description
Measured in mg/dL
Time Frame
3,6,9,12 months follow-up
Title
Change over time of echocardiographic effusion
Description
Measured in ml
Time Frame
3,6,9,12 months follow-up
Title
Incidence and severity of Adverse Events
Description
All adverse events (AEs) will be monitored and recorded to assess the tolerability and safety of the treatment.
Time Frame
3,6,9,12 months follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged≥18 years
Idiopathic recurrent pericarditis with at least 2 recurrences
Recurrent pericarditis defined as a first episode of acute pericarditis followed by recurrences (at least two recurrences for this study). First episode of pericarditis is diagnosed when at least two of the following criteria were present: pericarditis typical chest pain (sharp and pleuritic, improved by sitting up and leaning forward), pericardial friction rubs, widespread ST segment elevation or PR interval (PR) depressions not previously reported, and new or worsening pericardial effusion. Recurrence is diagnosed when chest pain recurs and one or more of the following signs is present: fever, pericardial friction rub, ECG changes, echocardiographic evidence of new or worsening pericardial effusion, and elevations in the white blood cell count, erythrocyte sedimentation rate or C-reactive protein. To be enrolled in this study, elevation of C-reactive protein is mandatory both in the first attack and in the following recurrences. The investigators differentiate recurrences from incessant pericarditis, term used to define patients with continued activity of pericarditis (with a symptom-free interval of < 6 weeks)
Specific aetiologies excluded, including tuberculous, neoplastic or purulent aetiologies, post-cardiac injury syndromes, and rheumatic autoimmune diseases.
Female subjects must be postmenopausal, or incapable of pregnancy or permanently sterile, or if of childbearing potential must agree to use highly-effective method of contraception.
Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule.
Exclusion Criteria:
Ophthalmologic contraindications
Structural heart disease
Corrected QT interval >440msec in men and >450msec in women
Left ventricular hypertrophy >13mm in men and >11mm in woman
Known allergy or intolerance to hydroxychloroquine
Life expectancy of < 12 months
Complex congenital heart disease
History of ventricular arrhythmias other than isolated extrasystoles
Women who are pregnant (as evidenced by pregnancy test if pre-menopausal)
Known channelopathy such as Brugada syndrome, long QT syndrome, or Catecholaminergic monomorphic ventricular tachycardia
On the heart transplant list
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
George Lazaros, MD, PhD, FESC
Phone
+306974389238
Email
glaz35@hotmail.com
Facility Information:
Facility Name
"Hippokration" General Hospital of Athens
City
Athens
State/Province
Attiki
ZIP/Postal Code
11527
Country
Greece
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Lazaros, MD, PhD, FESC
Email
glaz35@hotmail.com
First Name & Middle Initial & Last Name & Degree
George Lazaros, MD, PhD, FESC
First Name & Middle Initial & Last Name & Degree
Konstantinos Tsioufis, MD, PhD, FESC
First Name & Middle Initial & Last Name & Degree
Ioannis Doundoulakis, MD, MSc (Res)
First Name & Middle Initial & Last Name & Degree
Panagiotis Tsioufis, MD, MSc
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Hydroxychloroquine in Colchicine-Resistant Glucocorticoid-Dependent Idiopathic Recurrent Pericarditis
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