Influence of Rivaroxaban for Intermittent Claudication and Exercise Tolerance in Patients With Symptomatic PAD

NCT04305028 | Unknown FDA Drug

• 1 other identifier: 132/20
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of the conducted research is to evaluate the protective effect of rivaroxaban (trade name of the Xarelto medicinal product), administered together with acetylsalicylic acid (ASA), in comparison with the effectiveness of using ASA alone, in relation to the distance of claudication and exercise tolerance in patients with PAD over a period of 3 months. At present, COMPASS results show that rivaroxaban vascular dose (2.5 mg twice daily) in combination with ASA (75-100 mg once daily) provides more effective cardiovascular protection (defined as cardiovascular death, vascular, myocardial infarction and stroke) compared to ASA alone. So far, however, no scientific studies have been carried out into account the effect of the drug on the progress of PAD and exercise tolerance in patients.

Conditions

Peripheral Arterial Disease

Keywords

Peripheral Arterial Disease; Intermittent Claudication; Rivaroxaban

Outcome Measures

Primary Outcomes (8)

• Number of Participants Diagnosed with Stroke at 3 Months

  Number of participants diagnosed with ischemic or hemorrhagic stroke

  3 months

• Number of Participants Diagnosed with Myocardial Infarction (MI) at 3 Months

  Number of participants diagnosed with myocardial infarction

  3 months

• Number of Participants who Died from Cardiovascular Causes at 3 Months

  Number of participants who died because of Cardiovascular causes

  3 months

• Number of Participants who Died from Any Cause at 3 Months

  Number of Participants who died for any reason not related to accidents.

  3 months

• Number of Participants Diagnosed with Acute Limb Ischaemia (ALI) at 3 Months

  Number of participants diagnosed with acute limb ischaemia definied as limb threatening ischaemia with evidence of acute arterial obstruction by radiological criteria or a new pulse deficit leading to an intervention (ie, surgery, thrombolysis, peripheral angioplasty, or amputation.

  3 months

• Number of Participants Diagnosed with Major Limb Amputation (AMI) at 3 Months

  Number of participants diagnosed with major limb amputation defined as amputations due to a vascular event above the forefoot, or defined as minor amputation if involving the forefoot and digits.

  3 months

• Change From Baseline in the Distance of Intermittent Claudication (Δ Dch) at 3 Months

  Change in the distance of intermittent claudication in the test according to Gardner's protocol

  3 months

• Change From Baseline in the Maximal Distance of Intermittent Claudication (Δ Dmax) at 3 Months

  Change in the maximal distance of intermittent claudication in the test according to Gardner's protocol

  3 months

Other Outcomes (14)

• Number of Participants Diagnosed with Fatal Bleeding (FB) at 3 Months

  3 months

• Number of Participants Diagnosed with Non-Fatal Symptomatic Intracranial Haemorrhage (IH) at 3 Months

  3 months

• Number of Participants Diagnosed with Non-Fatal, Non-Intracranial Haemorrhage (Non-IH) Symptomatic Bleeding at 3 Months into a critical organ

  3 months

Study Arms (2)

Experimental: Rivaroxaban [2.5 mg] + Aspirin

Drug: Rivaroxaban 2.5 mg twice daily, tablet Drug: Aspirin 75-100 mg once daily, tablet

Drug: Rivaroxaban; Drug: Aspirin

Active Comparator: Aspirin

Drug: Aspirin 75-100 mg once daily, tablet

Drug: Aspirin

Interventions

Rivaroxaban DRUG

Rivaroxaban 2.5 MG (Xarelto) twice daily, tablet

Also known as: Rivaroxaban 2.5 MG, Xarelto

Experimental: Rivaroxaban [2.5 mg] + Aspirin

Aspirin DRUG

Aspirin 75-100 mg once daily, tablet

Also known as: Acetylsalicylic acid

Active Comparator: Aspirin; Experimental: Rivaroxaban [2.5 mg] + Aspirin

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The primary selection criterion for all respondents is the presence of PAD and the Caucasian ancestry. PAD patients with intermittent claudication and no clinical contraindications to the treadmill test will be enrolled in the study. Patients with PAD in Stage II Fountaine will be qualified for the study. The disease will be confirmed with an ankle-brachial index (ABI), with a result of less than 0.90. For all participants, ABI will be measured at the beginning of the study; the result will be calculated from the ratio of the highest systolic blood pressure on the limb to the highest systolic blood pressure on the shoulder.

You may qualify if:

• \. PAD, the Fontaine classification II

You may not qualify if:

• Severe heart failure with known ejection fraction \<30% or NYHA class III or IV symptoms
• High risk of bleeding
• Stroke with one month or any history of hemorrhaging or lacunar stroke
• Estimated glomerular filtration rate \<15 ml/ml
• Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy/, oral anticoagulant therapy/
• The known non-cardiovascular disease that is associated with poor prognosis (i.n, metastatic cancer)
• History of hypersensitivity or known contraindication for rivaroxaban, aspirin
• Systemic treatment with strong inhibitors of CYP 3A4 as well as p-glycoprotein or strong inducers of CYP 3M
• Any known hepatic disease associated with coagulopathy
• Concurrent participation in another study with an investigational drug
• Known contraindication to any study-related procedures\* Concerns: Absolute contraindications to an exercise test
• Respiratory failure
• BMI above or equal 40
• Musculoskeletal dysfunction preventing walking (e.g. amputations)

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead
• Poznan University of Physical Education: collaborator

Related Publications (16)

• Anand SS, Bosch J, Eikelboom JW, Connolly SJ, Diaz R, Widimsky P, Aboyans V, Alings M, Kakkar AK, Keltai K, Maggioni AP, Lewis BS, Stork S, Zhu J, Lopez-Jaramillo P, O'Donnell M, Commerford PJ, Vinereanu D, Pogosova N, Ryden L, Fox KAA, Bhatt DL, Misselwitz F, Varigos JD, Vanassche T, Avezum AA, Chen E, Branch K, Leong DP, Bangdiwala SI, Hart RG, Yusuf S; COMPASS Investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):219-229. doi: 10.1016/S0140-6736(17)32409-1. Epub 2017 Nov 10.

  PMID: 29132880 RESULT

• Borensztajn K, Peppelenbosch MP, Spek CA. Factor Xa: at the crossroads between coagulation and signaling in physiology and disease. Trends Mol Med. 2008 Oct;14(10):429-40. doi: 10.1016/j.molmed.2008.08.001. Epub 2008 Sep 4.

  PMID: 18774340 RESULT

• Borissoff JI, Spronk HM, Heeneman S, ten Cate H. Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc Res. 2009 Jun 1;82(3):392-403. doi: 10.1093/cvr/cvp066. Epub 2009 Feb 19.

  PMID: 19228706 RESULT

• Bires AM, Lawson D, Wasser TE, Raber-Baer D. Comparison of Bruce treadmill exercise test protocols: is ramped Bruce equal or superior to standard bruce in producing clinically valid studies for patients presenting for evaluation of cardiac ischemia or arrhythmia with body mass index equal to or greater than 30? J Nucl Med Technol. 2013 Dec;41(4):274-8. doi: 10.2967/jnmt.113.124727. Epub 2013 Nov 12.

  PMID: 24221922 RESULT

• CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.

  PMID: 8918275 RESULT

• Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, Metsarinne K, O'Donnell M, Dans AL, Ha JW, Parkhomenko AN, Avezum AA, Lonn E, Lisheng L, Torp-Pedersen C, Widimsky P, Maggioni AP, Felix C, Keltai K, Hori M, Yusoff K, Guzik TJ, Bhatt DL, Branch KRH, Cook Bruns N, Berkowitz SD, Anand SS, Varigos JD, Fox KAA, Yusuf S; COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):205-218. doi: 10.1016/S0140-6736(17)32458-3. Epub 2017 Nov 10.

  PMID: 29132879 RESULT

• Gardner AW, Skinner JS, Cantwell BW, Smith LK. Progressive vs single-stage treadmill tests for evaluation of claudication. Med Sci Sports Exerc. 1991 Apr;23(4):402-8.

  PMID: 2056896 RESULT

• Goszcz A, Woroń J, Kostka-Trąbka E. Farmakoterapia przewlekłego niedokrwienia kończyn dolnych (PAD). [Pharmacotherapy for chronic lower limb ischaemia (PAD)] Farm Współ 2009; 2: 91-96.

  RESULT

• Illnait J, Castano G, Alvarez E, Fernandez L, Mas R, Mendoza S, Gamez R. Effects of policosanol (10 mg/d) versus aspirin (100 mg/d) in patients with intermittent claudication: a 10-week, randomized, comparative study. Angiology. 2008 Jun-Jul;59(3):269-77. doi: 10.1177/0003319707306963. Epub 2008 Apr 2.

  PMID: 18388038 RESULT

• Micker M, Chęciński P, Synowiec T. Postępowanie w przewlekłym niedokrwieniu kończyn dolnych.[Treatment of chronic ischaemia in the lower extremitie] Przew Lek 2006; 5: 12-21.

  RESULT

• Mika P, Spannbauer A, Cencora A. Zmiana wzorca chodu i dystansu marszu w trakcie zapoznawania się pacjenta z chromaniem przestankowym ze specyfiką marszu na bieżni. [Change of the walking pattern and walking distance during the patient's acquaintance with the diaphragm cladication on the treadmill] Pielęg Chir Angiol 2009; 2: 65-69.

  RESULT

• Olinic DM, Tataru DA, Homorodean C, Spinu M, Olinic M. Antithrombotic treatment in peripheral artery disease. Vasa. 2018 Feb;47(2):99-108. doi: 10.1024/0301-1526/a000676. Epub 2017 Nov 21.

  PMID: 29160765 RESULT

• Płatek AE, Szymański FM. Riwaroksaban - nowy lek plejotropowy o szerokim spektrum działań [Riwaroxaban - a new broad spectrum pleiotropic drug] Choroby Serca i Naczyń 2019, tom 16, nr 1, 34-40,

  RESULT

• Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975 Mar;31(1):103-15.

  PMID: 1100130 RESULT

• Smarż K, Jaxa-Chamiec T, Budaj A. Metody oceny wydolności fizycznej pacjentów kardiologicznych - elektrokardiograficzny, spiroergometryczny i echokardiograficzny test wysiłkowy. [Methods of assessing physical fitness of cardiac patients - electrocardiographic, spiroergometric and echocardiographic exercise test.] Postępy Nauk Medycznych, t. XXVIII, nr 11B, 2015

  RESULT

• Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther. 1974 May;15(5):443-53. doi: 10.1002/cpt1974155443. No abstract available.

  PMID: 4597226 RESULT

Related Links

• Xarelto description

Biospecimen

Retention: SAMPLES WITH DNA

Blood -EDTA samples, Serum samples, DNA samples

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Interventions

Rivaroxaban; Aspirin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Zbigniew Krasiński, Prof, MD

  Poznan University of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Ewa Strauss, PhD

  Poznan University of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Zbigniew Krasiński, Prof, MD

CONTACT

+48 61 854 91 41; zkrasinski@ump.edu.pl

Ewa Strauss, Prof, MD

CONTACT

+48 696 115 255; estrauss@ump.edu.pl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: March 10, 2021
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2024
• Last Updated: March 10, 2021

Record last verified: 2021-03