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

Peripheral Arterial Disease Clinical Trial

— CADET-PAD  

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04277702
• Other study ID #: CADET-PAD
• Secondary ID: 2020-000715-71
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 2020
• Est. completion date: December 2023

Study information

• Verified date: February 2020
• Source: Jagiellonian University
• Contact: Pawel Maga, Prof
• Phone: +48692814418
• Email: maga.pawel[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: December 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Montelukast 10mg
Oral administration of 10mg of montelukast daily for 12 months

Procedure:
• Endovascular treatment
Percutaneous transluminal angioplasty combined with bare-metal stenting of lower limbs arteries

Drug:
• Standard anti-platelet treatment
Standard antithrombotic treatment for patients undergoing endovascular procedures

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Jagiellonian University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure of endovascular treatment (Target Vessel Failure)	Hemodynamically significant restenosis or reocclusion of the treated vessel	12 months
Secondary	Death		12 months
Secondary	Myocardial Infarction		12 months
Secondary	Stroke		12 months
Secondary	Combined MACEs	Occurrence of any major adverse cardiovascular event	12 months
Secondary	Treated limb amputation	Large amputation of the treated limb	12 months
Secondary	Significant decrease of life quality	Significant decrease of life quality in patients undergoing treatment measured by the Vascu-Qol and Walking Impairment Questionnaire	12 months