UMIN-CTR Clinical Trial

Public title

Evaluation of the efficacy of neuromuscular electrical stimulation in ICU patients undergoing continuous renal replacement therapy.

Acronym

Evaluation of the efficacy of neuromuscular electrical stimulation in ICU patients undergoing continuous renal replacement therapy.

Scientific Title

Evaluation of the efficacy of neuromuscular electrical stimulation in ICU patients undergoing continuous renal replacement therapy.

Scientific Title:Acronym

Evaluation of the efficacy of neuromuscular electrical stimulation in ICU patients undergoing continuous renal replacement therapy.

Region

Japan

Condition

Acute renal failure

Classification by specialty

Emergency medicine	Intensive care medicine	Rehabilitation medicine
Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To examine the effects of early neuromuscular electrical stimulation on quantitative and qualitative changes in muscle, physical function and physical, mental and cognitive function after discharge from hospital in patients undergoing continuous renal replacement therapy.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Quadriceps muscle thickness

Key secondary outcomes

Medical Research Council sum score, Functional Status Score for the ICU, handgrip strength, Short Physical Performance Battery, and Barthel Index.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Interventions/Control_1

Participants assigned to the NMES group received protocol-based early mobilization and rehabilitation plus bilateral lower-limb NMES for 30 minutes per day, 5 days per week, until ICU discharge.

Interventions/Control_2

Participants assigned to the control group received protocol-based early mobilization and rehabilitation without NMES or sham stimulation.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients admitted to ICU and receiving continuous renal replacement therapy

Key exclusion criteria

(i) Difficulty in standing prior to ICU admission.
(ii) Use of intra-aortic balloon pumping
(iii) Circulatory support by percutaneous cardiopulmonary support
(iv) Pacemaker placement (NMES group only) (v) Skin injury at the electrode site (NMES group only)
(5) Skin injury at the electrode site (NMES group only)
(vi) Presence of deep vein thrombosis (NMES group only)
(vii) Other patients deemed unsuitable as research subjects by the principal investigator.

Target sample size

40

Name of lead principal investigator

1st name	Tadayoshi
Middle name
Last name	Nonoyama

Organization

University of Fukui Hospital

Division name

Department of Rehabilitation

Zip code

9101193

Address

23-3, Matsuoka-Shimogozuki, Eiheiji-machi, Yoshida-gun, Fukui.

TEL

0776-61-3111

Email

nonoyama@u-fukui.ac.jp

Name of contact person

1st name	Tadayoshi
Middle name
Last name	Nonoyama

Organization

University of Fukui Hospital

Division name

Department of Rehabilitation

Zip code

9101193

Address

23-3, Matsuoka-Shimogozuki, Eiheiji-machi, Yoshida-gun, Fukui.

TEL

0776-61-3111

Homepage URL

Email

nonoyama@u-fukui.ac.jp

Institute

University of Fukui Hospital

Institute

Department

Personal name

Organization

Japanese Society of Physical Therapy

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

University of Fukui Hospital

Address

23-3, Matsuoka-Shimogozuki, Eiheiji-machi, Yoshida-gun, Fukui.

Tel

0776-61-3111

Email

nonoyama@u-fukui.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2022

Year

11

Month

28

Day

URL releasing protocol

The protocol is not publicly available.

Publication of results

Published

URL related to results and publications

No publicly accessible results URL is available.

Number of participants that the trial has enrolled

22

Results

Twenty-two participants were randomized (Control, 12; NMES, 10). Mean rectus femoris thickness change from baseline to Day 7 was -15.6% in Control (n=9) and -11.3% in NMES (n=10). The mean difference (NMES minus Control) was 4.3 percentage points (95% CI, -5.7 to 14.3; P=0.373). Nine participants received NMES, and no NMES-related adverse events occurred. Other adverse events were not systematically collected.

Results date posted

2026

Year

09

Month

12

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Twenty-two participants were randomized, but baseline data were available for 21 participants (Control, n=11; NMES, n=10) because one Control participant had no individual analytic record.

Overall, mean age was 72.9 years (SD 12.1), 17/21 participants (81.0%) were male, mean height was 160.7 cm (SD 10.6), mean admission body weight was 62.6 kg (SD 17.0), 8/21 (38.1%) had surgical admissions, mean APACHE II score was 20.7 (SD 4.1), mean Clinical Frailty Scale was 2.8 (SD 2.1; n=15), 7/21 (33.3%) received hemodialysis before admission, mean SOFA score was 9.5 (SD 2.4), and 11/21 (52.4%) received mechanical ventilation.

In Control, mean age was 71.8 years (SD 12.8), 9/11 (81.8%) were male, mean height was 160.1 cm (SD 10.7), mean admission body weight was 61.0 kg (SD 22.7), 3/11 (27.3%) had surgical admissions, mean APACHE II score was 21.8 (SD 3.5), mean Clinical Frailty Scale was 2.1 (SD 1.2; n=7), 4/11 (36.4%) received hemodialysis before admission, mean SOFA score was 9.7 (SD 2.5), and 6/11 (54.5%) received mechanical ventilation.

In NMES, mean age was 74.1 years (SD 11.8), 8/10 (80.0%) were male, mean height was 161.3 cm (SD 11.0), mean admission body weight was 64.2 kg (SD 8.1), 5/10 (50.0%) had surgical admissions, mean APACHE II score was 19.4 (SD 4.5), mean Clinical Frailty Scale was 3.4 (SD 2.6; n=8), 3/10 (30.0%) received hemodialysis before admission, mean SOFA score was 9.3 (SD 2.4), and 5/10 (50.0%) received mechanical ventilation.

Participant flow

Seventy-two patients were assessed for eligibility, and 50 were excluded: CRRT for less than 48 hours (n=11), inability to stand before admission (n=10), IABP or mechanical circulatory support (n=3), pacemaker (n=3), skin injury at an electrode site (n=1), deep vein thrombosis (n=1), declined consent (n=8), DNAR order (n=7), and other reasons (n=6).

Twenty-two participants were randomized to Control (n=12) or NMES (n=10). Nine NMES-assigned participants received NMES; one did not receive NMES because of clinical deterioration after enrollment.

The Day 7 primary analysis included 9 Control and 10 NMES participants. Three Control participants were unavailable because of no baseline measurement (n=1), no Day 7 measurement after death (n=1), or ICU death with no individual analytic record (n=1). Hospital-discharge muscle-thickness measurements were available for 8 Control and 8 NMES participants. The exploratory late-assessment analysis included 9 Control participants, including one last pre-death measurement, and 8 NMES participants. Missing values were not imputed.

Adverse events

Nine of 10 NMES-assigned participants received NMES, and no NMES-related adverse events occurred among the recipients (0/9). ICU death occurred in 3/12 Control participants (25.0%) and 2/10 NMES participants (20.0%). Other adverse events not temporally associated with NMES were not systematically collected as trial outcomes; therefore, a comprehensive between-group safety comparison was not performed.

Outcome measures

Analyses were performed using available cases without imputation. Values are means with SDs, and between-group differences are NMES minus Control.

Primary outcome: Rectus femoris thickness change from baseline to Day 7 was -15.6% (SD 11.0; n=9) in Control and -11.3% (SD 9.2; n=10) in NMES. The mean difference was 4.3 percentage points (95% CI, -5.7 to 14.3; P=0.373).

Exploratory late assessment: Rectus femoris thickness change was -27.3% (SD 8.9; n=9) in Control and -13.9% (SD 9.8; n=8) in NMES. The mean difference was 13.4 percentage points (95% CI, 3.7 to 23.1; P=0.010). This finding was exploratory because assessment timing varied and the Control group included one last pre-death measurement.

Secondary outcomes:
MRC sum score at ICU discharge was 50.4 (SD 9.0; n=8) in Control and 52.7 (SD 6.1; n=9) in NMES; difference 2.3 (95% CI, -5.9 to 10.5; P=0.555).
FSS-ICU at ICU discharge was 19.0 (SD 12.3; n=10) and 20.1 (SD 9.6; n=9); difference 1.1 (95% CI, -9.5 to 11.8; P=0.828).
Handgrip strength at ICU discharge was 12.7 kgf (SD 4.2; n=7) and 17.3 kgf (SD 6.7; n=9); difference 4.6 kgf (95% CI, -1.3 to 10.5; P=0.114).
Barthel Index at ICU discharge was 21.7 (SD 23.7; n=9) and 18.8 (SD 11.3; n=8); difference -2.9 (95% CI, -22.3 to 16.4; P=0.748).
MRC sum score at hospital discharge was 56.0 (SD 3.1; n=5) and 55.1 (SD 5.0; n=7); difference -0.9 (95% CI, -6.1 to 4.4; P=0.722).
Handgrip strength at hospital discharge was 16.1 kgf (SD 4.4; n=5) and 22.3 kgf (SD 7.8; n=6); difference 6.2 kgf (95% CI, -2.4 to 14.8; P=0.136).
SPPB at hospital discharge was 5.2 (SD 4.1; n=6) and 8.7 (SD 4.1; n=7); difference 3.5 (95% CI, -1.5 to 8.6; P=0.148).
Barthel Index at hospital discharge was 75.0 (SD 17.6; n=6) and 70.6 (SD 31.2; n=8); difference -4.4 (95% CI, -33.3 to 24.5; P=0.746).
Three-month Barthel Index was 92.5 (SD 15.0; n=4) in Control and 93.3 (SD 12.1; n=6) in NMES. No inferential comparison was performed because follow-up was sparse.
ICU-discharge SPPB and hospital-discharge FSS-ICU data were unavailable.

Plan to share IPD

No

IPD sharing Plan description

The deidentified individual participant data generated and analyzed during this study will not be shared.

Recruitment status

Terminated

Date of protocol fixation

2022

Year

11

Month

26

Day

Date of IRB

2022

Year

12

Month

06

Day

Anticipated trial start date

2023

Year

02

Month

01

Day

Last follow-up date

2025

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Recruitment was discontinued after 22 of the planned 40 participants had been enrolled because the principal investigator changed institutions, making further recruitment and follow-up operationally infeasible. The decision was unrelated to treatment effects or safety concerns.

Registered date

2022

Year

11

Month

27

Day

Last modified on

2026

Year

09

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000056272