Hydroxychloroquine for the Prevention of Cardiovascular Events in Myocardial Infarction Patients - a Safety Pilot Trial (OXI)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02648464 |
|
Recruitment Status :
Recruiting
First Posted : January 7, 2016
Last Update Posted : March 14, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Myocardial Infarction Acute Coronary Syndrome Inflammation Hydroxychloroquine Antirheumatic Agents Cardiovascular Diseases | Drug: Hydroxychloroquine Drug: Placebo | Phase 4 |
Anti-rheumatic medications decrease cardiovascular mortality in rheumatoid arthritis patients, based mainly on their anti-inflammatory effect. No studies have addressed their effect on preventing recurrent cardiovascular events among non-rheumatic patients.
In the pilot phase 200 myocardial infarction patients will be recruited during their index visit to the study hospitals. Patients will be randomized after initial coronary angiography to receive either hydroxychloroquine 300 mg a day or placebo during six months. Patients will be followed up until 12 months at four visits. Visit one is at doctor´s office at 3 to 5 weeks from the day of recruitment. Visit two is at study nurse´s office at 5.5 to 6 months. Visit three is a phone interview by the study nurse at 8.5 to 9.5 months. Visit four at 11.5 to 12.5 months is at doctor´s office.
This study evaluates the safety of hydroxychloroquine in the setting of myocardial infarction, and whether hydroxychloroquine treatment could reduce the incidence of recurrent cardiovascular events among myocardial infarction patients. Furthermore, the effect of hydroxychloroquine on cardiovascular risk factors and systemic inflammation parameters will be studied. In a subgroup of 40 patients, the effect of hydroxychloroquine on aortic inflammation will be assessed by PET/CT scan.
If this safety pilot study with 200 patients proves successful (i.e. no major complications), 2500 patients will be recruited in additional centers in Finland and the Nordic Countries.
Orion Pharma provides the active hydroxychloroquine tablet (Oxiklorin) but provides no other assistance or funding for the study.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 200 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Hydroxychloroquine for the Prevention of Recurrent Cardiovascular Events in Myocardial Infarction Patients - a Safety Pilot Trial |
| Study Start Date : | February 2016 |
| Estimated Primary Completion Date : | December 2019 |
| Estimated Study Completion Date : | December 2019 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Hydroxychloroquine
Hydroxychloroquine 300 mg tablet by mouth daily for 6 months. Patients under the weight of 60 kg: hydroxychloroquine 300 mg tablet daily for 5 days per week for 6 months.
|
Drug: Hydroxychloroquine
Other Name: Oxiklorin |
|
Placebo Comparator: Placebo
Placebo tablet by mouth daily for 6 months. Patients under the weight of 60 kg: placebo tablet daily for 5 days per week for 6 months.
|
Drug: Placebo |
- Rate of major cardiovascular adverse events [ Time Frame: Twelve months ]Myocardial infarction, hospitalization for unstable angina, and heart failure
- Rate of the primary endpoint plus stroke and urgent coronary revascularization [ Time Frame: Twelve months ]
- Effect on the incidence of type 2 diabetes and the level of Hba1c [ Time Frame: Six months ]
- Effect on cholesterol levels [ Time Frame: Six months ]The effect of hydroxychloroquine on total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels
- Effect on high-sensitivity C-reactive protein (hs-CRP) level [ Time Frame: Six months ]
- Effect on soluble biomarkers of inflammation [ Time Frame: Six months ]Frozen samples (plasma and whole blood) will be stored for future evaluation of biomarkers related to inflammation and cardiovascular disease, such as tumor necrosis factor alpha, interleukin 6 (IL-6), IL-1beta, IL-18, and messenger ribonucleic acid (mRNA) analyses.
- Effect on aortic inflammation assessed by PET / CT scan [ Time Frame: Six months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients must have high-sensitivity troponin or CKMB above the upper limit of normal with at least one of the following criteria:
-
Anginal symptoms suggestive of cardiac ischemia
- Accelerating pattern of anginal pain (episodes of angina that have at least 5 minutes duration and are more frequent, severe, longer in duration and/or precipitated by less exertion).
- Prolonged (>20 minutes) or recurrent anginal pain at rest or with minimal effort.
- Anginal pain at rest or with minimal exertion, and at least 20 minutes of duration, occurring >48 hours after an acute Q-wave myocardial infarction.
-
ECG criteria
- New, persistent or transient ST-segment depression >0,1 mV (0,08 seconds after the J-point) in at least 2 extremity leads or 3 precordial leads.
- New, persistent or transient ST-segment elevation in two contiguous leads ≥0.2 mV in men or ≥0.15 mV in women in leads V2-V3, and/or ≥0.1 mV in other leads.
Patients will be enrolled within 96 hours of coronary angiography
Exclusion Criteria:
- Contraindication for hydroxychloroquine (porphyria, psoriasis, retinopathy, hypersensitivity)
- Rheumatoid arthritis or other rheumatic disease
- Significant neuropathy of any cause
- Cardiomyopathy (diagnosed before the onset of index hospitalization)
- Muscle disease (that could worsen by the use of hydroxychloroquine)
- Pregnant or nursing women, and women of childbearing potential without efficient contraceptives.
- Angina precipitated by obvious provoking factors
- Prolonged ECG's corrected QT interval (>480 ms)
- Ongoing antibiotic therapy of any duration
- Uncontrolled severe cardiac arrhythmia resulting in hemodynamic instability
- Severe hepatic failure (alanine transaminase or gamma-glutamyltransferase ≥2 times above normal limits or international normalized ratio (INR) >1,5 and patient not using warfarin, and due to other than cardiac reasons).
- Renal failure, glomerular filtration rate <50 ml/min/1,73m2
- Hemoglobin <100 g/l (if not possible to correct with transfusion)
- Planned percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)
- Index myocardial infarction due to PCI or CABG restenosis.
- Inability to interpret ST-T segment changes on ECG (e.g. complete left bundle branch block or paced rhythm)
- Prior thrombolytic therapy (within 12 hours)
- Inability to give informed consent
- Fulminant vomiting or other disability to give oral medication
- Over 80 years of age
- Life expectancy less than one year
- Receiving another investigational drug within 4 weeks prior to the study. (Patients who have participated in investigational trials before the 4-week time period may be randomized as long as they have reached the primary endpoint).
- Patients with any other medical condition which, in the investigator's opinion, would interfere with optimal participation in the study or produce a significant risk to the patient
In addition, patients are not eligible for the PET/CT subgroup if they have received statin-therapy in the last 2 months prior to the hospitalization (i.e. statin therapy started during the index hospitalization is not an exclusion criteria).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02648464
| Contact: Otto Hartman, MD | otto.hartman@helsinki.fi |
| Finland | |
| Helsinki University Central Hospital | Recruiting |
| Helsinki, Finland, 00290 | |
| Contact: Otto Hartman, MD otto.hartman@helsinki.fi | |
| Haartman Hospital | Active, not recruiting |
| Helsinki, Finland | |
| North Karelia Central Hospital | Recruiting |
| Joensuu, Finland | |
| Contact: Tuomas Rissanen, MD | |
| Kymenlaakso Central Hospital | Recruiting |
| Kotka, Finland | |
| Contact: Jaana Yrjölä, MD | |
| Päijät-Häme Central Hospital | Recruiting |
| Lahti, Finland | |
| Contact: Heli Tolppanen, MD | |
| South Karelia Central Hospital | Recruiting |
| Lappeenranta, Finland | |
| Contact: Tuomo Nieminen, Professor | |
| South Ostrobotnia Central Hospital | Recruiting |
| Seinäjoki, Finland | |
| Contact: Ismo Anttila, MD | |
| Study Director: | Juha Sinisalo, Professor | Helsinki University Central Hospital |
Publications:
| Responsible Party: | Otto Hartman, MD, Helsinki University Central Hospital |
| ClinicalTrials.gov Identifier: | NCT02648464 |
| Other Study ID Numbers: |
2015-000233-73 |
| First Posted: | January 7, 2016 Key Record Dates |
| Last Update Posted: | March 14, 2018 |
| Last Verified: | March 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Study data is planned to be available at the study organization´s website, and by specific request from the investigator |
|
Hydroxychloroquine anti-inflammatory Myocardial infarction cardiovascular diseases |
|
Myocardial Infarction Acute Coronary Syndrome Inflammation Infarction Cardiovascular Diseases Pathologic Processes Ischemia Necrosis Myocardial Ischemia Heart Diseases |
Vascular Diseases Hydroxychloroquine Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents |