COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients

Not Applicable

Withdrawn

• Conditions: NSTEMI
• Interventions: Drug: Placebo; Drug: Colchicine

• Registration Number: NCT02095522
• Lead Sponsor: Tel-Aviv Sourasky Medical Center

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.

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-06
• Study First Submitted QC: 2014-03-20
• Study First Posted: 2014-03-24
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-06
• Last Update Posted: 2016-07-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 1mg per day
Colchicine	Colchicine	Colchicine 1mg per day for one month

Primary Outcome Measures

Name	Time	Method
Improvement of RH-PAT at 1 month (a marker of endothelial function)	1 month	RH-PAT will be measured before the angiography and after one month.

Secondary Outcome Measures

Name	Time	Method
Improvement in endothelial function markers.	1 month	serum ICAM VACAM and endothelin will be measured
inflammatory biomarkers Improvement of heart rate variability (HRV)	1 month
Improvement in inflammatory biomarkers (before cardiac catheterization, after cardiac catheterization and at 1 month time follow-up)	1 month	biomarkers will be assessed before and after the angiography. Comparison of the biomarker levels will be assessed between the two treatment groups
Changes in cholinergic status	1 month	serum ACHE will be measured at randomization and after one month
Reduction of Acute Kidney Injury post PCI	1 month	AKI will be defined per AKIN as an increase of 0.3mg/dl. The two treatment groups will be compared
Reduction in radial artery occlusion	acute
Reduction of peri-procedural myocardial infarction	1 month
Major adverse clinical events (MACE) defined as a composite of all-cause mortality, myocardial infarction, repeat revascularization, and 30 day readmission rate	1 month
quality of life under colchicine treatment	1 month	The investigators will assess this outcome using a standard quality of life questionnaire (EQ5).
Safety	up to 1 year	Safety will be assessed by comparing adverse events between the two groups

Trial Locations

Locations (2)

Tel Aviv Medical Center; 🇮🇱 Tel Aviv, Israel

Sourasky medical center (Ichilov); 🇮🇱 Tel-Aviv, Israel