PAD Screening Study

NCT05584072 | Unknown

• 1 other identifier: 2021.208
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral arterial disease (PAD) due to atherosclerotic narrowing of arteries of the lower limb is common and associated with increased cardiovascular mortality and morbidity. The prevalence of PAD increases with age affecting approximately 10% of population age \>60 years and nearly 50% age \>85 years. However, the awareness of PAD is poor with less than 5% of patients with PAD aware of their condition; and the condition is often underdiagnosed and undertreated. Clinical diagnosis of PAD can be difficult because up to 50% of patients do not complain of overt symptoms such as intermittent claudication (IC) and critical limb ischemia (CLI). The prognosis of patients with PAD is not benign irrespective of symptoms. Atherosclerosis is a systemic disease where 30% to 50% of patients with PAD have concomitant coronary artery disease (CAD) and cerebrovascular disease (CVD) and they share common risk factors including diabetes mellitus, hyperlipidemia and hypertension. In the multi-national REACH registry, 1 in 5 patients with PAD experienced CV death, MI, stroke, or hospitalization within 1 year which is even higher than patients with CAD or CVD. Screening may increase early detection of PAD and provide opportunity to identify concomitant CV diseases and/or risk factors, earlier treatment and hence reduction. in adverse CV events. However, there is lack of an accurate and cost-effective assessment tool for PAD screening. Resting Ankle-Brachial Index (ABI) which measures the difference in blood pressure between the arm and the ankle as a ratio is the most widely used method to diagnose PAD. An ABI \<0.9 is diagnostic of obstructive lower limb PAD with sensitivity of 97% and a specificity of 80-100%. ABI performed with exercise (i.e. exercise ABI) has been shown to increase the diagnostic yield of resting ABI when the clinical suspicion for PAD is high and the resting ABI is normal. Exercise is usually performed with a treadmill or active pedal plantar-flexion (APP) when patient is unable to walk on the treadmill. Resting and exercise ABI measurement can be performed in an outpatient setting but is time consuming, and requires technical training and special equipment such as Doppler ultrasonic velocity signal probe which is not readily available in the primary care setting. This has led to under-utilization of ABI for the diagnosis of PAD despite strong guideline recommendations and unsuitable as a screening tool in the primary care setting. Other diagnostic tests for PAD such as duplex ultrasound, magnetic resonance or computed tomography angiography are even less readily accessible, costly and can potentially causes harm to patients in the form of radiation and contrast reaction. Questionnaires such as the Rose Questionnaire or Edinburgh Questionnaire have been validated to identify PAD patients with claudication symptoms. Although these questionnaires have high specificity of \>90%, their sensitivity is much lower at 20-30%.They are also time consuming to administer at scale in the outpatient setting. Therefore, questionnaires alone are not widely adopted for PAD screening in the primary care setting. Recently, a single claudication question has been proposed as a simpler and easier to administer screening tool for PAD which has high specificity but is also limited by low sensitivity.Therefore, there is an unmet clinical need for an alternative assessment tool for PAD screening that is more sensitive than currently available claudication questionnaires and can be easily administered in the primary care setting. In this study, we aim to evaluate the diagnostic accuracy of a novel assessment tool consisting of a single claudication question combined with symptom-limited APP test in detection of PAD using resting and/or exercise ABI as the reference. This screening tool is simple to use and has the potential to be self administered without supervision whereby reducing time and costs of screening.

Conditions

Peripheral Arterial Disease

Keywords

claudication; pedal plantarflexion test; peripheral arterial disease

Outcome Measures

Primary Outcomes (1)

• sensitivity and specificity of the combined PAD assessment tool

  The primary end points are sensitivity and specificity of the combined PAD assessment tool, which will be used to estimate the positive predictive value and negative predictive value (with 95% confidence intervals) of each and both component of the combined assessment tool to detect PAD with reference to ABI in the overall population, and in pre-defined subgroup stratified by their predicted risk group as per AHA ASCVD risk estimator.

  24 hours

Study Arms (1)

Active pedal plantarflexion (APP) test

Diagnostic Test: Active pedal plantarflexion (APP) test

Interventions

Active pedal plantarflexion (APP) test DIAGNOSTIC_TEST

Active pedal plantarflexion (APP) test

Active pedal plantarflexion (APP) test

Eligibility Criteria

• Age: 45 Years - 79 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Assuming the prevalence of PAD to be 8% in this group of patients, the sensitivity of the new assessment tool to be 50%, and the specificity to be 90%, an estimate of 341 patients will be required to show that the new self-assessment is better than the claudication questionnaire which is estimated to have a 20%-30% sensitivity and 90% specificity, with a 5% significance level and 80% power. Assuming the screening failure and drop-out rate to be 30%, we will need to screen at least 500 patients.

You may qualify if:

• \. patients of age 45-79

You may not qualify if:

• known diagnosis of PAD,
• History of revascularization for PAD,
• History of critical limb ischemia,
• History of amputation,
• Inability to perform active pedal plantarflexion test with guidance,
• Inability to answer the claudication question,
• Inability to give consent.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• Professor Bryan Ping Yen YAN (byan): collaborator

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Shatin, 0000, Hong Kong

RECRUITING

Related Publications (22)

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  PMID: 17543683 RESULT

• Wang Z, Wang X, Hao G, Chen Z, Zhang L, Shao L, Tian Y, Dong Y, Zheng C, Kang Y, Gao R; China hypertension survey investigators. A national study of the prevalence and risk factors associated with peripheral arterial disease from China: The China Hypertension Survey, 2012-2015. Int J Cardiol. 2019 Jan 15;275:165-170. doi: 10.1016/j.ijcard.2018.10.047. Epub 2018 Oct 25.

  PMID: 30389296 RESULT

• Sigvant B, Lundin F, Wahlberg E. The Risk of Disease Progression in Peripheral Arterial Disease is Higher than Expected: A Meta-Analysis of Mortality and Disease Progression in Peripheral Arterial Disease. Eur J Vasc Endovasc Surg. 2016 Mar;51(3):395-403. doi: 10.1016/j.ejvs.2015.10.022. Epub 2016 Jan 6.

  PMID: 26777541 RESULT

• Joosten MM, Pai JK, Bertoia ML, Rimm EB, Spiegelman D, Mittleman MA, Mukamal KJ. Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men. JAMA. 2012 Oct 24;308(16):1660-7. doi: 10.1001/jama.2012.13415.

  PMID: 23093164 RESULT

• Steg PG, Bhatt DL, Wilson PW, D'Agostino R Sr, Ohman EM, Rother J, Liau CS, Hirsch AT, Mas JL, Ikeda Y, Pencina MJ, Goto S; REACH Registry Investigators. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA. 2007 Mar 21;297(11):1197-206. doi: 10.1001/jama.297.11.1197.

  PMID: 17374814 RESULT

• Weitz JI, Byrne J, Clagett GP, Farkouh ME, Porter JM, Sackett DL, Strandness DE Jr, Taylor LM. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996 Dec 1;94(11):3026-49. doi: 10.1161/01.cir.94.11.3026. No abstract available.

  PMID: 8941154 RESULT

• Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 Mar 21;135(12):e686-e725. doi: 10.1161/CIR.0000000000000470. Epub 2016 Nov 13.

  PMID: 27840332 RESULT

• Yao ST, Hobbs JT, Irvine WT. Ankle systolic pressure measurements in arterial disease affecting the lower extremities. Br J Surg. 1969 Sep;56(9):676-9. doi: 10.1002/bjs.1800560910. No abstract available.

  PMID: 5808379 RESULT

• Guo X, Li J, Pang W, Zhao M, Luo Y, Sun Y, Hu D. Sensitivity and specificity of ankle-brachial index for detecting angiographic stenosis of peripheral arteries. Circ J. 2008 Apr;72(4):605-10. doi: 10.1253/circj.72.605.

  PMID: 18362433 RESULT

• Aboyans V, Criqui MH, Abraham P, Allison MA, Creager MA, Diehm C, Fowkes FG, Hiatt WR, Jonsson B, Lacroix P, Marin B, McDermott MM, Norgren L, Pande RL, Preux PM, Stoffers HE, Treat-Jacobson D; American Heart Association Council on Peripheral Vascular Disease; Council on Epidemiology and Prevention; Council on Clinical Cardiology; Council on Cardiovascular Nursing; Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Measurement and interpretation of the ankle-brachial index: a scientific statement from the American Heart Association. Circulation. 2012 Dec 11;126(24):2890-909. doi: 10.1161/CIR.0b013e318276fbcb. Epub 2012 Nov 16. No abstract available.

  PMID: 23159553 RESULT

• Ouriel K, McDonnell AE, Metz CE, Zarins CK. Critical evaluation of stress testing in the diagnosis of peripheral vascular disease. Surgery. 1982 Jun;91(6):686-93.

  PMID: 7079971 RESULT

• McPhail IR, Spittell PC, Weston SA, Bailey KR. Intermittent claudication: an objective office-based assessment. J Am Coll Cardiol. 2001 Apr;37(5):1381-5. doi: 10.1016/s0735-1097(01)01120-2.

  PMID: 11300450 RESULT

• Mohler ER 3rd, Treat-Jacobson D, Reilly MP, Cunningham KE, Miani M, Criqui MH, Hiatt WR, Hirsch AT. Utility and barriers to performance of the ankle-brachial index in primary care practice. Vasc Med. 2004 Nov;9(4):253-60. doi: 10.1191/1358863x04vm559oa.

  PMID: 15678616 RESULT

• Davies JH, Kenkre J, Williams EM. Current utility of the ankle-brachial index (ABI) in general practice: implications for its use in cardiovascular disease screening. BMC Fam Pract. 2014 Apr 17;15:69. doi: 10.1186/1471-2296-15-69.

  PMID: 24742018 RESULT

• Nicolai SP, Kruidenier LM, Rouwet EV, Bartelink ML, Prins MH, Teijink JA. Ankle brachial index measurement in primary care: are we doing it right? Br J Gen Pract. 2009 Jun;59(563):422-7. doi: 10.3399/bjgp09X420932.

  PMID: 19520025 RESULT

• Kieback AG, Espinola-Klein C, Lamina C, Moebus S, Tiller D, Lorbeer R, Schulz A, Meisinger C, Medenwald D, Erbel R, Kluttig A, Wild PS, Kronenberg F, Kroger K, Ittermann T, Dorr M. One simple claudication question as first step in Peripheral Arterial Disease (PAD) screening: A meta-analysis of the association with reduced Ankle Brachial Index (ABI) in 27,945 subjects. PLoS One. 2019 Nov 4;14(11):e0224608. doi: 10.1371/journal.pone.0224608. eCollection 2019.

  PMID: 31682633 RESULT

• Hoyer C, Sandermann J, Petersen LJ. The toe-brachial index in the diagnosis of peripheral arterial disease. J Vasc Surg. 2013 Jul;58(1):231-8. doi: 10.1016/j.jvs.2013.03.044. Epub 2013 May 18.

  PMID: 23688630 RESULT

• Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000 Jan;31(1 Pt 2):S1-S296. No abstract available.

  PMID: 10666287 RESULT

• Koon CM, Wing-Shing Cheung D, Wong PH, Wat E, Ng SK, Cheung WH, Fu-Yuen Lam F, Chook P, Fung KP, Leung PC, Yan BP. Salviae miltiorrhizae radix and puerariae lobatae radix herbal formula improves circulation, vascularization and gait function in a peripheral arterial disease rat model. J Ethnopharmacol. 2021 Jan 10;264:113235. doi: 10.1016/j.jep.2020.113235. Epub 2020 Aug 7.

  PMID: 32777518 RESULT

• Yan BP, Lau JY, Yu CM, Au K, Chan KW, Yu DS, Ma RC, Lam YY, Hiatt WR. Chinese translation and validation of the Walking Impairment Questionnaire in patients with peripheral artery disease. Vasc Med. 2011 Jun;16(3):167-72. doi: 10.1177/1358863X11404934.

  PMID: 21636675 RESULT

• Yan BP, Zhang Y, Kong AP, Luk AO, Ozaki R, Yeung R, Tong PC, Chan WB, Tsang CC, Lau KP, Cheung Y, Wolthers T, Lyubomirsky G, So WY, Ma RC, Chow FC, Chan JC; Hong Kong JADE Study Group. Borderline ankle-brachial index is associated with increased prevalence of micro- and macrovascular complications in type 2 diabetes: A cross-sectional analysis of 12,772 patients from the Joint Asia Diabetes Evaluation Program. Diab Vasc Dis Res. 2015 Sep;12(5):334-41. doi: 10.1177/1479164115590559. Epub 2015 Jul 3.

  PMID: 26141965 RESULT

• Dong M, Jiang X, Liao JK, Yan BP. Elevated rho-kinase activity as a marker indicating atherosclerosis and inflammation burden in polyvascular disease patients with concomitant coronary and peripheral arterial disease. Clin Cardiol. 2013 Jun;36(6):347-51. doi: 10.1002/clc.22118. Epub 2013 Mar 28.

  PMID: 23553913 RESULT

Related Links

• Hong Kong Monthly Digest of Statistics

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Condition Hierarchy (Ancestors)

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

Central Study Contacts

GuangMing Tan, MD

CONTACT

85255699658; gtan@cuhk.edu.hk

Daniel Xu

CONTACT

852 7382 1748; xjldaniel@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: October 18, 2022
• Study Start: June 10, 2021
• Primary Completion: May 31, 2023
• Study Completion: December 30, 2023
• Last Updated: October 18, 2022

Record last verified: 2022-10

Locations

HK (1)