Clinical trial NCT02095522: COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients
Official title: Does COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients?: A Prospective Randomized, Double-blind Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: NSTEMI
Keywords: colchicine NSTEMI endothelial function inflammation
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Tel Aviv Medical Center
First posted: 2014-03-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Colchicine has antiinflammatory properties. It has been shown to be effective in improving outcome in stable coronary disease. The exact mechanism is unclear. Study objective: to assess the effect of colchicine on endothelial function using the EndoPAT™ in NSTEMI Patients.

Study Hypothesis: There will be a significant difference on the RH-PAT levels of the patients who were in treated with colchicine versus the placebo group Study design and patient Selection One hundred and forty patients with the diagnosis of Non ST Elevation Myocardial Infarction will be enrolled to a prospective randomized double-blind placebo controlled study in Tel Aviv Medical Center, Tel Aviv, Israel. Patients will be recruited during their hospitalization before cardiac catheterization. All patients will sign an informed consent.

Primary outcome will be the improvement in endothelial function between baseline and after 1 month in both groups

Detailed description: Study design and patient Selection One hundred and forty patients with the diagnosis of Non ST Elevation Myocardial Infarction (NSTEMI) will be enrolled to a prospective randomized double-blind placebo controlled study in Tel Aviv Medical Center, Tel Aviv, Israel. Patients will be recruited during their hospitalization before cardiac catheterization. All patients will sign an inform consent. Study will be published on NIH clinicaltrials.com database.

Inclusion and exclusion criteria are presented in Table 1 Table 1: Patient Selection Inclusion criteria

1. NSTEMI Diagnosis 2. Patients above the age of 18 3. Informed consent Exclusion criteria

1. Hemodynamic instability
2. Pregnant women
3. Peripheral vascular disease with feeble or absent peripheral pulses
4. Restlessness and/or chaotic breathing
5. Renal dialysis
6. Severe aortic valve insufficiency/Stenosis
7. Severe mitral valve insufficiency
8. Congenital cardiac malformations (structural heart diseases)
9. Known extra-cardiac shunts
10. Major surgery within 30 days
11. Any medical condition that would impair participation (e.g. progressive neurological disorders, mental illness)
12. Known intolerance to colchicine
13. Ejection fraction less than 35% or past admission for CHF exacerbation in the last 30 days.
14. Inflammatory diseases
15. Current treatment with steroids, NSAID, chemotherapy or biologic medications

Pre Study exam

After enrollment, patients will undergo the following baseline procedure:

1. Physical examination and medical interview
2. Endothelial function using the EndoPat® before planned cardiac catheterization
3. Blood tests- see below for description

Blood sampling An 18-gauge cannula will be placed in an antecubital vein for blood sampling. Blood sample analyses will be performed using reagents, calibrators and control materials from Bayer Diagnostics (Berkshire, England) on the ADVIA 1650. A 40 ml blood sample will be obtained as described below. Blood tests timing is detailed at the end in the flow chart.

Each Patient will provide 40ml of blood for the following blood tests

1. Full chemistry including: lipid levels, thyroid function, liver enzymes function, Troponin, CPK, HbA1c, uric acid, and glucose levels.
2. Blood count
3. Inflammatory biomarker (hs-CRP, fibrinogen, IL-6, IL-1B, IL-18, MMP, Lp-PLA2, procalcitonin, IL-10, IL-35, TNFa, AchE, , PAI-1, MPO, cholinergic status. etc.)
4. Endothelial function markers: Endothelin-1, I-CAM, V-CAM, superoxide dismutase ADMA, and oxidized LDL
5. Serum Samples will be stored for future testing.

PAT score:

Peripheral arterial tonometry signals will be obtained using the EndoPAT 2000 device (Itamar Medical Inc., Caesarea, Israel), which has been validated and used previously to assess peripheral arterial tone in other populations. 14-17 Briefly, EndoPAT bio-sensors are placed on the index fingers of both arms. EndoPAT quantifies the endothelium-mediated changes in vascular tone, elicited by a 5-minute occlusion of the brachial artery (using a standard blood pressure cuff). When the cuff is released, the surge of blood flow causes an endothelium-dependent Flow Mediated Dilatation (FMD). The dilatation, manifested as reactive hyperemia, is captured by EndoPAT as an increase in the PAT Signal amplitude. A post-occlusion to pre-occlusion ratio is calculated by the EndoPAT software, providing the EndoPAT index. In addition, the EndoPAT system will measure heart rate variability.

Eligibility criteria: Inclusion Criteria:

1. NSTEMI Diagnosis
2. Patients above the age of 18
3. Informed consent

Exclusion Criteria:

1. Hemodynamic instability
2. Pregnant women
3. Peripheral vascular disease with feeble or absent peripheral pulses
4. Restlessness and/or chaotic breathing
5. Renal dialysis
6. Severe aortic valve insufficiency/Stenosis
7. Severe mitral valve insufficiency
8. Congenital cardiac malformations (structural heart diseases)
9. Known extra-cardiac shunts
10. Major surgery within 30 days
11. Any medical condition that would impair participation (e.g. progressive neurological disorders, mental illness)
12. Known intolerance to colchicine
13. Ejection fraction less than 35% or past admission for CHF exacerbation in the last 30 days.
14. Inflammatory diseases
15. Current treatment with steroids, NSAID, chemotherapy or biologic medications

Primary outcomes:
measure: Improvement of RH-PAT at 1 month (a marker of endothelial function)
timeFrame: 1 month
Secondary outcomes:
measure: Improvement in inflammatory biomarkers (before cardiac catheterization, after cardiac catheterization and at 1 month time follow-up)
timeFrame: 1 month
measure: Improvement in endothelial function markers.
timeFrame: 1 month
measure: inflammatory biomarkers Improvement of heart rate variability (HRV)
timeFrame: 1 month
measure: Changes in cholinergic status
timeFrame: 1 month
measure: Reduction of Acute Kidney Injury post PCI
timeFrame: 1 month
measure: Reduction in radial artery occlusion
timeFrame: acute
measure: Reduction of peri-procedural myocardial infarction
timeFrame: 1 month
measure: Major adverse clinical events (MACE) defined as a composite of all-cause mortality, myocardial infarction, repeat revascularization, and 30 day readmission rate
timeFrame: 1 month
measure: quality of life under colchicine treatment
timeFrame: 1 month
measure: Safety
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical Center
city: Tel-Aviv
country: Israel
facility: Sourasky medical center (Ichilov)
Study officials:
affiliation: Tel Aviv Medical Center
name: Yaron Arbel, MD
role: PRINCIPAL_INVESTIGATOR
References: