COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients

NSTEMI Clinical Trial

— CODEN  

Official title:

Does COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients?: A Prospective Randomized, Double-blind Placebo Controlled Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02095522
• Other study ID #: TASMC-13-YA-0636-CTIL
• Status: Withdrawn
• Phase: N/A
• First received: March 6, 2014
• Last updated: July 6, 2016
• Start date: March 2014
• Est. completion date: January 2016

Study information

• Verified date: July 2016
• Source: Tel-Aviv Sourasky Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• NSTEMI

Intervention

Drug:
• Colchicine
Colchicine 1mg per day for one month
• Placebo
Placebo

Locations

Country	Name	City	State
Israel	Tel Aviv Medical Center	Tel Aviv
Israel	Sourasky medical center (Ichilov)	Tel-Aviv

Sponsors (2)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center	Tel Aviv Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of RH-PAT at 1 month (a marker of endothelial function)	RH-PAT will be measured before the angiography and after one month.	1 month	No
Secondary	Improvement in inflammatory biomarkers (before cardiac catheterization, after cardiac catheterization and at 1 month time follow-up)	biomarkers will be assessed before and after the angiography. Comparison of the biomarker levels will be assessed between the two treatment groups	1 month	No
Secondary	Improvement in endothelial function markers.	serum ICAM VACAM and endothelin will be measured	1 month	No
Secondary	inflammatory biomarkers Improvement of heart rate variability (HRV)		1 month	Yes
Secondary	Changes in cholinergic status	serum ACHE will be measured at randomization and after one month	1 month	No
Secondary	Reduction of Acute Kidney Injury post PCI	AKI will be defined per AKIN as an increase of 0.3mg/dl. The two treatment groups will be compared	1 month	No
Secondary	Reduction in radial artery occlusion		acute	No
Secondary	Reduction of peri-procedural myocardial infarction		1 month	No
Secondary	Major adverse clinical events (MACE) defined as a composite of all-cause mortality, myocardial infarction, repeat revascularization, and 30 day readmission rate		1 month	No
Secondary	quality of life under colchicine treatment	The investigators will assess this outcome using a standard quality of life questionnaire (EQ5).	1 month	Yes
Secondary	Safety	Safety will be assessed by comparing adverse events between the two groups	up to 1 year	Yes