Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 6 of 13 for:    oxi

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02648464
Recruitment Status : Completed
First Posted : January 7, 2016
Last Update Posted : June 9, 2020
Sponsor:
Collaborators:
Finnish Foundation for Cardiovascular Research
Orion Corporation, Orion Pharma
Aarne Koskelo Foundation
Finnish Cultural Foundation
Information provided by (Responsible Party):
Otto Hartman, Helsinki University Central Hospital

Tracking Information
First Submitted Date  ICMJE December 18, 2015
First Posted Date  ICMJE January 7, 2016
Last Update Posted Date June 9, 2020
Actual Study Start Date  ICMJE February 1, 2016
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2020)
Rate of major cardiovascular adverse events [ Time Frame: Twelve months ]
Myocardial infarction, mortality, hospitalization for unstable angina, and heart failure
Original Primary Outcome Measures  ICMJE
 (submitted: January 5, 2016)
Rate of major cardiovascular complications [ Time Frame: Six months ]
Investigate whether hydroxychloroquine reduces the rate of death, myocardial infarction, unstable angina pectoris requiring hospitalization, and urgent coronary revascularization among acute coronary syndrome patients.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2016)
  • Rate of the primary endpoint plus stroke [ Time Frame: Nine 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydroxychloroquine for the Prevention of Cardiovascular Events in Myocardial Infarction Patients - a Safety Pilot Trial
Official Title  ICMJE Hydroxychloroquine for the Prevention of Recurrent Cardiovascular Events in Myocardial Infarction Patients - a Safety Pilot Trial
Brief Summary This safety pilot study evaluates the effect of hydroxychloroquine on preventing recurrent cardiovascular events among myocardial infarction patients. Half of the participants will receive hydroxychloroquine, whereas the other half will receive placebo during six months.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Myocardial Infarction
  • Acute Coronary Syndrome
  • Inflammation
  • Hydroxychloroquine
  • Antirheumatic Agents
  • Cardiovascular Diseases
Intervention  ICMJE
  • Drug: Hydroxychloroquine
    Other Name: Oxiklorin
  • Drug: Placebo
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Hydroxychloroquine
  • 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.
    Intervention: Drug: Placebo
Publications * Hartman O, Kovanen PT, Lehtonen J, Eklund KK, Sinisalo J. Hydroxychloroquine for the prevention of recurrent cardiovascular events in myocardial infarction patients: rationale and design of the OXI trial. Eur Heart J Cardiovasc Pharmacother. 2017 Apr 1;3(2):92-97. doi: 10.1093/ehjcvp/pvw035.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 6, 2020)
125
Original Estimated Enrollment  ICMJE
 (submitted: January 5, 2016)
200
Actual Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients must have high-sensitivity troponin or CKMB above the upper limit of normal with at least one of the following criteria:

  1. Anginal symptoms suggestive of cardiac ischemia

    1. 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).
    2. Prolonged (>20 minutes) or recurrent anginal pain at rest or with minimal effort.
    3. 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.
  2. ECG criteria

    1. 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.
    2. 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).

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Finland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02648464
Other Study ID Numbers  ICMJE 2015-000233-73
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Responsible Party Otto Hartman, Helsinki University Central Hospital
Study Sponsor  ICMJE Helsinki University Central Hospital
Collaborators  ICMJE
  • Finnish Foundation for Cardiovascular Research
  • Orion Corporation, Orion Pharma
  • Aarne Koskelo Foundation
  • Finnish Cultural Foundation
Investigators  ICMJE
Study Director: Juha Sinisalo, Professor Helsinki University Central Hospital
PRS Account Helsinki University Central Hospital
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP