Clinical trial NCT04277702: Cysteinyl Leukotriene Antagonist in Atherosclerosis Inhibition in Patients After Endovascular Treatment Due to Peripheral Arterial Disease
Official title: The Assessment of Cysteinyl Leukotriene Receptor Antagonist Role in Inhibition of Atherosclerosis, Proliferation and Its Influence on Endothelial Function in Patients Undergoing Endovascular Treatment Due to Peripheral Arterial Disease.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Peripheral Arterial Disease
Peripheral Vascular Diseases
Lower Limb Ischemia
Atherosclerosis of Artery
Keywords: atherosclerosis
Peripheral Arterial Disease
Montelukast
Leukotrienes
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
First posted: 2020-02-20
Enrollment: 200
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Failure of endovascular treatment (Target Vessel Failure)
timeFrame: 12 months
Secondary outcomes:
measure: Death
timeFrame: 12 months
measure: Myocardial Infarction
timeFrame: 12 months
measure: Stroke
timeFrame: 12 months
measure: Combined MACEs
timeFrame: 12 months
measure: Treated limb amputation
timeFrame: 12 months
measure: Significant decrease of life quality
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Angiology Department, Jagiellonian University Medical College
name: Pawel Maga, Prof
role: PRINCIPAL_INVESTIGATOR
References: