COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients (CODEN)

Tel Aviv Sourasky Medical Center

Status: Withdrawn

Conditions: NSTEMI

Treatments: Drug: Colchicine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02095522

TASMC-13-YA-0636-CTIL

Details and patient eligibility

About

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

Full 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

2. Hemodynamic instability

3. Pregnant women

4. Peripheral vascular disease with feeble or absent peripheral pulses

5. Restlessness and/or chaotic breathing

6. Renal dialysis

7. Severe aortic valve insufficiency/Stenosis

8. Severe mitral valve insufficiency

9. Congenital cardiac malformations (structural heart diseases)

10. Known extra-cardiac shunts

11. Major surgery within 30 days

12. Any medical condition that would impair participation (e.g. progressive neurological disorders, mental illness)

13. Known intolerance to colchicine

14. Ejection fraction less than 35% or past admission for CHF exacerbation in the last 30 days.

15. Inflammatory diseases

16. 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 2 patient groups, including a placebo group

Colchicine

Experimental group

Description:

Colchicine 1mg per day for one month

Treatment:

Drug: Colchicine

Placebo

Placebo Comparator group

Description:

Placebo 1mg per day

Treatment:

Drug: Placebo