Pericarditis Idiopathic RecurrentPhase 3RESTORENCT05737680
Hydroxychloroquine in Colchicine-Resistant Glucocorticoid-Dependent Idiopathic Recurrent Pericarditis
A Phase 3 study testing Hydroxychloroquine and Colchicine in people with Pericarditis Idiopathic Recurrent, run by Hippocration General Hospital at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pericarditis Idiopathic Recurrent
- What is being tested?
- Hydroxychloroquine and Colchicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGreece
- Study dates
- Feb 2023to Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Greece1 site
"Hippokration" General Hospital of Athens
Athens, Attica, 11527
George Lazaros, MD, PhD, FESC, glaz35@hotmail.com
George Lazaros, MD, PhD, FESC
About this study
Official title: Efficacy and Safety of Hydroxychloroquine in Colchicine-RESistant Glucocorticoid-DependenT IdiOpathic REcurrent Pericarditis: A Randomized Clinical Trial (The RESTORE Randomized Clinical Trial)
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).
Read the 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.
- Conditions
- Pericarditis Idiopathic Recurrent
- Being tested
- Hydroxychloroquine, Colchicine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine 400mg daily
ColchicineDrug
Colchicine continued
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine arm | Active comparator | Hydroxychloroquine 400mg daily Receives: Drug: Hydroxychloroquine |
| Colchicine arm | Active comparator | Colchicine continued Receives: Drug: Colchicine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months follow-up
Secondary outcomes (7)
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.
Measured: 12 months follow-up
Dose of the Corticosteroid in the time of the recurrence
Measured: 12 months follow-up
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.
Measured: 3,6,9,12 months follow-up
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.
Measured: 3,6,9,12 months follow-up
Change over time of C-reactive protein levels
Measured in mg/dL
Measured: 3,6,9,12 months follow-up
Change over time of echocardiographic effusion
Measured in ml
Measured: 3,6,9,12 months follow-up
Incidence and severity of Adverse Events
All adverse events (AEs) will be monitored and recorded to assess the tolerability and safety of the treatment.
Measured: 3,6,9,12 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study startFeb 2023 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pericarditis Idiopathic RecurrentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hippocration General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Konstantinos Tsioufis, Hippocration General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737680
- Sponsor's protocol ID
- RESTORE
- Acronym
- RESTORE
- Status last verified
- Feb 2023
- First submitted
- 30 Jan 2023
- Last updated
- 22 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Hydroxychloroquine in Colchicine-RESistant Glucocorticoid-DependenT IdiOpathic REcurrent Pericarditis: A Randomized Clinical Trial (The RESTORE Randomized Clinical Trial)
- ClinicalTrials.gov ID
- NCT05737680
- Acronym / sponsor ID
- RESTORE / RESTORE
- Conditions
- Pericarditis Idiopathic Recurrent
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hippocration General HospitalUniversity, hospital or other
- Study start
- Feb 2023 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine arm | Active comparator | Drug: HydroxychloroquineHydroxychloroquine 400mg daily |
| Colchicine arm | Active comparator | Drug: ColchicineColchicine continued |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineHydroxychloroquine 400mg daily | Drug | Hydroxychloroquine arm |
| ColchicineColchicine continued | Drug | Colchicine arm |
Primary outcome
Recurrence Rate
Time frame: 12 months follow-up
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.
7 secondary outcomes
Time to Pericarditis Recurrence
Time frame: 12 months follow-up
Dose of the Corticosteroid in the time of the recurrence
Time frame: 12 months follow-up
State-Trait Anxiety Inventory (STAI)
Time frame: 3,6,9,12 months follow-up
Change over time of pericardial pain
Time frame: 3,6,9,12 months follow-up
Change over time of C-reactive protein levels
Time frame: 3,6,9,12 months follow-up
Change over time of echocardiographic effusion
Time frame: 3,6,9,12 months follow-up
Incidence and severity of Adverse Events
Time frame: 3,6,9,12 months follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine and Colchicine in people with Pericarditis Idiopathic Recurrent, run by Hippocration General Hospital at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact George Lazaros, MD, PhD, FESC (+306974389238, glaz35@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence Rate (time frame: 12 months follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.