Cysteinyl Leukotriene Antagonist in Atherosclerosis Inhibition in Patients After Endovascular Treatment Due to Peripheral Arterial Disease

NCT ID: NCT04277702

Last Updated: 2020-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-31

Study Completion Date

2023-12-31

Brief Summary

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Atherosclerosis is a civilization disease, which pathophysiology is based on chronic inflammatory response in the wall of vessels that is caused by increase of pro-inflammatory substances. It is a significant challenge for diagnostics and pharmacology. This disease occurs in over 60% of the population over 70 years old. There are many factors that are responsible for this process including group of the arachidonic acid metabolism products - leukotriens, especially leukotriene E4 (LTE4). The effect of these factors was described as the base of pathology not only cardiovascular diseases but also the base of development of asthma and other allergic diseases. The substance which blocks the activity of these factors - montelukast - is a common method of treatment in asthma.

The aim of this project is to investigate the influence of cysteinyl leukotriens receptor antagonists on lower limb arteries reocclusion rate in patients with peripheral artery disease (PAD) after endovascular treatment.

During previous years we conducted a prospective study, which helped us evaluating the dynamics of leukotriens and thromboxane levels in patients with PAD, who underwent endovascular treatment - peripheral transluminal angioplasty (PTA). We established for the first time the dependence between the increased level of LTE4 in urine (uLTE4) and restenosis or reocclusion occurrence, which translates to the necessity of further procedures and a decrease in the quality of life. We should ask ourselves a question: Is blocking of cysteinyl leukotriens reaction as proinflammatory and proliferative factors, by the use of receptor CysLT1 antagonists going to decrease the quantity of restenosis and reocclusions after endovascular treatment? Within the project performed in the Angiology Department of Jagiellonian University among the patients suffering from PAD and fulfilling all inclusion criteria, the randomized double-blinded clinical study will be performed. Patients will be assigned to two groups: Treatment Group (which will be receiving cysteinyl leukotriene antagonist (montelukast) in a dose of 10mg/day for 12 months) and Control Group to which placebo will be administered. Among all patients population, at every visit at 1., 3., 6., and 12-month clinical state, ultrasound, hemodynamic parameters, and endothelium imaging will be performed as well as uLTE4 measurements. A comparison of the results between both groups will give us an answer if blocking uLTE4 receptors may become a breakthrough in future atherosclerosis treatment.

The mechanisms, which lead to restenosis is still not fully understood, and currently used methods of treatment - antiplatelets, anti-proliferative drugs, and anticoagulants - are not fully effective. Thanks to this research the knowledge about treatment and prevention of atherosclerosis will be increased, which will be connected with future better patient care, especially patients with PAD.

Detailed Description

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Conditions

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Peripheral Arterial Disease Peripheral Vascular Diseases Lower Limb Ischemia Atherosclerosis of Artery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Montelukast + standard treatment

Group Type EXPERIMENTAL

Montelukast 10mg

Intervention Type DRUG

Oral administration of 10mg of montelukast daily for 12 months

Endovascular treatment

Intervention Type PROCEDURE

Percutaneous transluminal angioplasty combined with bare-metal stenting of lower limbs arteries

Standard anti-platelet treatment

Intervention Type DRUG

Standard antithrombotic treatment for patients undergoing endovascular procedures

Placebo+ standard treatment

Group Type PLACEBO_COMPARATOR

Endovascular treatment

Intervention Type PROCEDURE

Percutaneous transluminal angioplasty combined with bare-metal stenting of lower limbs arteries

Standard anti-platelet treatment

Intervention Type DRUG

Standard antithrombotic treatment for patients undergoing endovascular procedures

Interventions

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Montelukast 10mg

Oral administration of 10mg of montelukast daily for 12 months

Intervention Type DRUG

Endovascular treatment

Percutaneous transluminal angioplasty combined with bare-metal stenting of lower limbs arteries

Intervention Type PROCEDURE

Standard anti-platelet treatment

Standard antithrombotic treatment for patients undergoing endovascular procedures

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients with peripheral arterial disease qualified for endovascular treatment with Rutherford 3 or 4 clinical symptoms.
2. Age 45 - 75 years old.
3. Signed informed consent.

Exclusion Criteria

1. Patients with peripheral arterial disease (PAOD) with Rutherford 1,2,5 or 6 clinical symptoms.
2. Age \< 45 or \> 75 years old.
3. Infection and/or fever (temperature above 37,2 C) within the last 3 weeks preceding the study recruitment (viral infections, cold, sinusitis) and use of antibiotics within the last 2 months.
4. Symptoms of acute tissue infection
5. Chronic inflammatory disease (e.g. COPD stage \>II in GOLD classification)
6. HIV+, HCV+, HBS+.
7. Autoimmunological diseases and use of steroids or immunosuppressive medications within the last 3 months.
8. Inflammatory blood vessel disorders (with exception of atherosclerosis)
9. Myocardial infarction or stoke within last 6 months.
10. Buerger Disease.
11. Chronic heart failure (3-4 NYHA)
12. Acute lower limb ischemia or surgical revascularization within last 6 months.
13. Serious trauma or surgery procedure within last 6 months.
14. Asthma.
15. On-going antileukotriene treatment.
16. Neoplasm diagnosed within 5 years.
17. Chronic Kidney Disease (creat. \>177 µmol/l).
18. Pregnancy, puerperium, women without efficient contraception.
19. Vaccinations within 30 days before recruitment.
20. Hospitalisation in intensive care unit within 3 months.
21. Lack of the possibility of the follow-up participation.
Minimum Eligible Age

45 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jagiellonian University

OTHER

Sponsor Role lead

Responsible Party

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Pawel Maga

Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pawel Maga, Prof

Role: PRINCIPAL_INVESTIGATOR

Angiology Department, Jagiellonian University Medical College

Central Contacts

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Pawel Maga, Prof

Role: CONTACT

+48692814418

Other Identifiers

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2020-000715-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CADET-PAD

Identifier Type: -

Identifier Source: org_study_id

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