Does Neuromuscular Electrical Stimulation Improve the Absolute Walking Distance in Patients With Intermittent Claudication Compared to Best Available Treatment?

A Multicenter Randomised Controlled Study: Does Neuromuscular Electrical Stimulation Improve the Absolute Walking Distance in Patients With Intermittent Claudication (NESIC) Compared to Best Available Treatment?

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03446027

Acronym

NESIC

Enrollment

200

Registered

2018-02-26

Start date

2018-02-16

Completion date

2021-09-30

Last updated

2024-04-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Intermittent Claudication, Peripheral Vascular Diseases

Brief summary

Intermittent claudication (IC) is caused by a blockage in the artery of the leg, causing muscle pain. Although some evidence of the efficacy of neuromuscular electrical stimulation (NMES) in the management of patients with IC exists, further high quality research is required. This proposed study is vital to identify the contribution of clinical change using NMES, compared to the current gold standard recommended practice of supervised exercise therapy (SET) and, actual standard of care offered in the majority of the UK and Ireland, including best medical therapy (BMT). The device is expected to increase the walking distance in patients with intermittent claudication (IC), and therefore have a benefit on the same when provided in addition to supervised exercise programmes. It is also expected to cause a reduction in pain symptoms and reduced likelihood of major intervention in late stage peripheral arterial disease (PAD). The principal research objective is to assess the clinical efficacy of a neuromuscular electrical stimulation (NMES) device as an adjunct to the local standard care that is available at the study randomisation sites, in order to improve walking distance in patients with intermittent claudication (IC).

Interventions

DEVICENMES

NMES device to be used for up to 3 hours daily in 30 minute sessions for 3 months.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Capacity to provide informed consent * Aged 18 or above * Positive Edinburgh Claudication Questionnaire * ABPI \<0.9 OR positive stress test (fall in ankle pressure \>30mmHg, 40 secs post 1 min treadmill at 10% gradient, 4 km/h)

Exclusion criteria

* Severe IC requiring invasive intervention as determined by the treating clinician * Critical limb Ischaemia as defined by the European Consensus Document * Co-morbid disease prohibiting walking on a treadmill or taking part in supervised exercise therapy. * Popliteal entrapment syndrome * Commenced vascular symptom specific medication in previous 6 months e.g. naftidrofuryl oxalate, cilostazol * Pregnancy * Any implanted electronic, cardiac or defibrillator device * Acute deep vein thrombosis * Broken or bleeding skin including leg ulceration * Peripheral neuropathy * Recent lower limb injury or lower back pain

Design outcomes

Primary

Measure	Time frame	Description
Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups	3 months	Measured by treadmill testing. Absolute walking distance in meters at baseline and 3 months

Secondary

Measure	Time frame	Description
Compliance With Interventions - Exercise Advice (EA)	3 months	Comparison of compliance with exercise advice as per local standard of care.
Device Experience Questionnaire - Reduces Leg Pain	3 months	To report ease of device use and suggest any developments.
Device Experience Questionnaire - Increased Walk Distance	3 months	To report ease of device use and suggest any developments.
Device Experience Questionnaire - Used as Instructed	3 months	To report ease of device use and suggest any developments.
Device Experience Questionnaire - Could Have Used More	3 months	To report ease of device use and suggest any developments.
Device Experience Questionnaire - Used After Treatment	3 months	To report ease of device use and suggest any developments.
Difference in the Initial Claudication Distance (ICD) at 3 Months Between the Two Treatment Groups	3 months	Measured by treadmill testing. ICD in meters at baseline and 3 months
Quality of Life - Intermittent Claudication Questionnaire (ICQ)	Baseline, 3 months, 6 months, 12 months	Patient questionnaire. Used to assess change in disease-specific QoL.
Quality of Life - EuroQoL 5D (EQ5D) Health Scale	Baseline, 3 month, 6 month and 12 months	Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement.
Quality of Life Short Form 36 (SF-36) Physical Component Summary	Baseline, 3 month, 6 month and 12 months	Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement.
Haemodynamic Assessment - Duplex Ultrasonography - Difference in Volume Flow Between Baseline and 3 Months	3 months	Using an arterial ultrasound probe and pre-set volume flow algorithms on a duplex ultrasound machine, flow within the common femoral artery (CFA), of the most affected limb, will be measured, approximately 5cm below the mid-inguinal point at the groin. Measures include volume flow (VF, cc/min) to assess whether using the device increases this measurement.
Haemodynamic Assessment - Laser Doppler Flowmetry (LDF) - Difference in Blood Flux Between Baseline and 12 Months	Baseline, 3 month, 6 month and 12 months	The single fibre laser optical probe of the LDF machine will be positioned on the dorsal aspect of the foot using single use adhesive pads. Flux, as a measure of superficial skin blood flow will be measured to assess whether using the device increases this measurement.
Haemodynamic Assessment - Difference in Ankle Brachial Pressure Index (ABPI) - Left - Between Baseline and 12 Months	Baseline, 3 month, 6 month and 12 months	The brachial blood pressure from the right arm using a manual blood pressure monitor cuff and Doppler will be recorded after 5 minutes of resting supine on a couch. The systolic blood pressure of the anterior tibial artery and posterior tibial artery at the ankle will also be recorded using the cuff and Dopplermethod. The ratio of the systolic brachial and ankle pressures will form the ABPI measurement.
Health Economic Assessment	Baseline, 3 month, 6 month and 12 months	The economic analyses will compare local therapy (supervised exercise therapy (SET) or exercise advice (EA) only) versus the intervention (local therapy + Neuromuscular Electrical Stimulation, NMES) in patients with Intermittent Claudication. The analyses will be based on a (i) patient level in-trial cost-effectiveness analysis, (ii) a decision model and (iii) budget impact assessment. The in-trial analysis will calculate quality-adjusted life years (QALYs) over the one year time horizon of the trial.
Device Experience Questionnaire - Ease of Use	3 months	To report ease of device use and suggest any developments.
Quality of Life - EuroQoL 5D (EQ5D) Health Index	Baseline, 3 months, 6 months, 12 months	Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement.
Quality of Life Short Form 36 (SF-36) Mental Component Summary	Baseline, 3 months, 6 months, 12 months	Patient questionnaire. Used to assess the generic QoL and will allow economic assessment based on intervention and score improvement.
Haemodynamic Assessment - Duplex Ultrasonography - Difference in Time Average Mean Velocity Between Baseline and 3 Months	3 months	Using an arterial ultrasound probe and pre-set volume flow algorithms on a duplex ultrasound machine, flow within the common femoral artery (CFA), of the most affected limb, will be measured, approximately 5cm below the mid-inguinal point at the groin. Measures include time-averaged mean volume (TAMV, cm/s) to assess whether using the device increases this measurement.
Haemodynamic Assessment - Difference in Ankle Brachial Pressure Index (ABPI) - Right - Between Baseline and 12 Months	Baseline, 3 months, 6 months and 12 months	The brachial blood pressure from the right arm using a manual blood pressure monitor cuff and Doppler will be recorded after 5 minutes of resting supine on a couch. The systolic blood pressure of the anterior tibial artery and posterior tibial artery at the ankle will also be recorded using the cuff and Dopplermethod. The ratio of the systolic brachial and ankle pressures will form the ABPI measurement.
Compliance With Interventions - Supervised Exercise Therapy (SET)	3 months	Comparison of compliance with SET classes.
Compliance With Interventions - Neuromuscular Electrical Stimulation (NMES)	3 months	Compliance with NMES device. NMES compliance data collected from the data logger fitted to device and patient diary will be combined to report overall compliance.

Other

Measure	Time frame	Description
Sub-group Analysis 3 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+BMT vs BMT)	3 months	Subgroup analysis 3: Right censored Tobit regression model for the AWD at 3 months to assess the effects of NMES in the non-SET sites (NMES+BMT vs BMT).
Sub-group Analysis 4 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+BMT vs. SET+BMT)	3 months	Subgroup analysis 4: Right censored Tobit regression model for AWD at 3 months to assess the effects of (NMES+BMT) has a similar effect as (SET+BMT).
Sub-group Analysis 5 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+SET+BMT vs. NMES+BMT)	3 months	Subgroup analysis 5: Determine if (NMES+SET+BMT) is more effective than (NMES+BMT).
Sub-group Analysis 1 - Difference in Absolute Walking Difference Between Baseline and 3 Months SET Sites vs Non-SET Sites	3 months	Subgroup analysis 1: Right censored Tobit regression model for AWD at 3 months to assess the effects SET sites vs non-SET sites (NMES+SET+BMT & SET+BMT vs NMES+BMT & BMT).
Sub-group Analysis 2 - Difference in Absolute Walking Difference Between Baseline and 3 Months (NMES+SET+BMT vs SET+BMT)	3 months	Subgroup analysis 2: Right censored Tobit Regression model for AWD at 3 months to assess the effects of NMES in the SET sites (NMES+SET+BMT vs SET+BMT).

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
Control There will be no change to the local site standard of care for patients with IC attributed to participation in this trial. Those sites with Supervised Exercise Therapy (SET) will continue to provide this intervention as per their normal standard of care and locally agreed protocol.	98
Device Local therapy + Neuromuscular Electrical Stimulation (NMES) NMES: NMES device to be used for up to 3 hours daily in 30 minute sessions for 3 months.	92
Total	190

Baseline characteristics

Characteristic	Control	Device	Total
Age, Continuous	67.44 years STANDARD_DEVIATION 9.44	68.17 years STANDARD_DEVIATION 8.84	67.79 years STANDARD_DEVIATION 9.13
Body Mass Index	28.63 kg/m^2 STANDARD_DEVIATION 6.66	28.10 kg/m^2 STANDARD_DEVIATION 5.12	28.37 kg/m^2 STANDARD_DEVIATION 5.95
Medical history Angina	13 participants	10 participants	23 participants
Medical history Angio revascularisation	25 participants	14 participants	39 participants
Medical history Bypass revascularisation	12 participants	5 participants	17 participants
Medical history Diabetes	26 participants	21 participants	47 participants
Medical history Heart attack	17 participants	15 participants	32 participants
Medical history High cholesterol	64 participants	68 participants	132 participants
Medical history Hypertension	63 participants	65 participants	128 participants
Medical history Stroke	9 participants	9 participants	18 participants
Medication Anticoagulant	15 participants	10 participants	25 participants
Medication Antihypertensives	65 participants	66 participants	131 participants
Medication Antiplatelets	79 participants	75 participants	154 participants
Medication Lipid modification therapy	81 participants	80 participants	161 participants
Performance limited due to intermittent claudication A little	9 participants	7 participants	16 participants
Performance limited due to intermittent claudication A lot	4 participants	3 participants	7 participants
Performance limited due to intermittent claudication Missing	7 participants	2 participants	9 participants
Performance limited due to intermittent claudication Not at all	9 participants	12 participants	21 participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	3 Participants	3 Participants	6 Participants
Race (NIH/OMB) Black or African American	3 Participants	1 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	90 Participants	87 Participants	177 Participants
Retired No	29 participants	24 participants	53 participants
Retired Yes	69 participants	68 participants	137 participants
Sex: Female, Male Female	28 Participants	22 Participants	50 Participants
Sex: Female, Male Male	70 Participants	70 Participants	140 Participants
Smoking status Current smoker	34 participants	22 participants	56 participants
Smoking status Former smoker	58 participants	64 participants	122 participants
Smoking status Never	6 participants	6 participants	12 participants
Work status Higher managerial and professional occupations	5 participants	3 participants	8 participants
Work status Intermediate occupations (e.g. clerical, sales, service)	4 participants	5 participants	9 participants
Work status Lower managerial and professional occupations	1 participants	8 participants	9 participants
Work status Lower supervisory and technical occupations	1 participants	1 participants	2 participants
Work status Never worked or long-term unemployed	7 participants	2 participants	9 participants
Work status Routine occupations	6 participants	4 participants	10 participants
Work status Semi-routine occupations	2 participants	1 participants	3 participants
Work status Small employers and own account workers	3 participants	0 participants	3 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 102	2 / 98
other Total, other adverse events	44 / 102	47 / 98
serious Total, serious adverse events	13 / 102	11 / 98

Outcome results

Primary

Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups

Measured by treadmill testing. Absolute walking distance in meters at baseline and 3 months

Time frame: 3 months

Population: Control group includes both BMT and BMT + SET and the treatment group includes NMES + BMT and NMES + BMT + SET Included participants with both baseline and 3 month treadmill data.

Arm	Measure	Group	Value (MEAN)	Dispersion
Control	Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups	3 months	327.74 Meters	Standard Deviation 222.65
Control	Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups	Baseline	220.12 Meters	Standard Deviation 148.27
Device	Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups	Baseline	242.97 Meters	Standard Deviation 187.08
Device	Difference in the Absolute Walking Distance (AWD) at 3 Months Between the Two Treatment Groups	3 months	370.38 Meters	Standard Deviation 251.38

Comparison: Right censored Tobit regression model for AWD at 3 months for the ITT population.~Difference between arms (between baseline and 3 months) - the primary analysis estimates the difference in the AWD at 3 months between the two treatment groups control vs. device. Control group includes both BMT and BMT + SET and the treatment group includes NMES + BMT and NMES + BMT + SET Included participants with both baseline and 3 month treadmill data.p-value: 0.2895% CI: [-0.674, 2.343]Tobit Regression

Secondary

Compliance With Interventions - Exercise Advice (EA)

Comparison of compliance with exercise advice as per local standard of care.

Time frame: 3 months

Population: EA (part of BMT): compliant if completed 75% or more of recommended level of EA (75% of minutes performing exercises recommended by centre).~Data for this Outcome Measure was pre-specified to be collected and assessed as a single group irrespective of intervention Arm/Group.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Control	Compliance With Interventions - Exercise Advice (EA)	Complier	99 Participants
Control	Compliance With Interventions - Exercise Advice (EA)	Non-complier	52 Participants
Control	Compliance With Interventions - Exercise Advice (EA)	Missing	39 Participants

Secondary

Compliance With Interventions - Neuromuscular Electrical Stimulation (NMES)

Compliance with NMES device. NMES compliance data collected from the data logger fitted to device and patient diary will be combined to report overall compliance.

Time frame: 3 months

Population: NMES: compliant if completed 75% or more of recommended level of NMES usage.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Control	Compliance With Interventions - Neuromuscular Electrical Stimulation (NMES)	Complier	68 Participants
Control	Compliance With Interventions - Neuromuscular Electrical Stimulation (NMES)	Non-complier	12 Participants
Control	Compliance With Interventions - Neuromuscular Electrical Stimulation (NMES)	Missing	12 Participants

Secondary

Compliance With Interventions - Supervised Exercise Therapy (SET)

Comparison of compliance with SET classes.

Time frame: 3 months

Population: Participant's who attended SET programme.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Control	Compliance With Interventions - Supervised Exercise Therapy (SET)	Complier	69 Participants
Control	Compliance With Interventions - Supervised Exercise Therapy (SET)	Non-complier	19 Participants
Control	Compliance With Interventions - Supervised Exercise Therapy (SET)	Missing	11 Participants

Secondary