Effectiveness of Rehabilitation Nursing versus Usual Therapist-Led Treatment in Patients with Acute Ischemic Stroke: A Randomized Non-Inferiority Trial

Figures & data

Figure 1 Flow chart of participants.

Abbreviations: mITT, modified intention-to-treat, all participants followed the random allocation with outcome data; PP, per-protocol, participants followed the random allocation with outcome data and attending the final outcome assessment.

Table 1 Baseline Demographic and Clinical Characteristics Between Groups

Variables	Experimental Group (n = 108)	Control Group (n = 101)	P value
Age (yrs), mean ± SD	64.35 ± 10.59	61.36 ± 15.27	0.287
Male, n (%)	79 (73.1%)	68 (67.3%)	0.686
Stratification indicator, n (%)			0.459
wCST-LL<2mL	59 (54.6%)	50 (49.5%)
wCST-LL≥2mL	49 (45.4%)	51 (50.5%)
Time from onset to enrollment (d), mean ± SD	3.81 ± 1.61	4.07 ± 1.81	0.492
Muscle strength on hemiplegic side, median (IQR)
Upper limb	2.00 (1.00–4.00)	2.00 (0.50–4.00)	0.772^‡
Lower limb	3.00 (2.00–4.00)	3.00 (2.00–4.00)	0.510^‡
Education, n (%)			0.071^‡
Illiteracy	10 (9.3%)	11(10.9%)
Primary school	33 (30.6%)	36 (35.6%)
Junior high school	33 (30.6%)	33 (32.7%)
High school/technical secondary school	20 (18.5%)	20 (19.8%)
College degree and above	12 (11.2%)	1 (1.0%)
Insurance, n (%)			0.779
Local medical insurance	53 (48.9%)	55 (54.5%)
Offsite medical insurance	36 (33.3%)	27 (26.7%)
No medical insurance	19 (17.6%)	19 (18.8%)
Risk factors, n (%)
Smoking	49 (45.4%)	44 (43.6%)	0.793
Family history of cardiovascular and cerebrovascular diseases	6 (5.6%)	8 (7.9%)	0.494
TIA	1 (0.9%)	2 (2.0%)	0.953^†
Hypertension	73 (67.6%)	70 (69.3%)	0.790
Diabetes mellitus	28 (25.9%)	33 (32.7%)	0.284
Atrial fibrillation	3 (2.8%)	9 (8.9%)	0.057^†
Coronary heart disease	5 (4.6%)	4 (4.0%)	0.811^†
Hyperhomocysteinemia	23 (21.3%)	21 (20.8%)	0.929
Hyperlipidemia	19 (17.6%)	19 (18.8%)	0.819
MAS, median (IQR)	12.00 (4.00–24.80)	11.00 (3.00–24.50)	0.604
FMA, median (IQR)	28.50 (17.00–53.80)	30.00 (12.00–53.50)	0.603
ARAT, median (IQR)	1.00 (0.00–26.80)	0.00 (0.00–28.50)	0.673
MBI, median (IQR)	29.50 (20.70–50.00)	28.00 (20.00–55.00)	0.929^‡
NIHSS, median (IQR)	6.00 (4.00–9.00)	6.00 (3.00–10.00)	0.613^‡
mRS, median (IQR)	4.00 (4.00–4.00)	4.00 (4.00–4.00)	0.992

Notes: ^†Fisher exact probability method; ^‡Mann–Whitney U-test.

Abbreviations: wCST-LL, weighted corticospinal tract lesion load; TIA, transient ischemic attacks; MAS, Motor Assessment Scale; FMA, Fugl-Meyer Assessment; ARAT, Action Research Arm Test; MBI, modified Barthel Index; NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale; SD, standard deviation; IQR, interquartile range.

Table 2 Between-Group Difference on Primary Outcomes After 7 Days Treatment (PP Analysis, n=200)

Outcome Measure	Experimental Group (n = 105)	Control Group (n = 95)	Noninferiority 1-Tailed Test^a			Superiority 2-Tailed Test^b
			Non-Inferiority Margin (δ)	Z	P value	Z	P value
MAS	24.00 (9.00–38.00)	13.00 (5.00–32.00)	6.94	−5.222	<0.001*	−2.174	0.030
FMA	51.00 (20.50–79.00)	33.00 (17.00–68.00)	12.00	−4.929	<0.001*	−1.982	0.047
ARAT	17.00 (0.00–39.00)	0.00 (0.00–34.00)	10.00	−6.245	<0.001*	−1.913	0.056
Change in MAS	5.00 (1.50–14.00)	3.00 (0.00–7.00)	2.15	−5.815	<0.001*	−3.012	0.003*
Change in FMA	7.50 (1.25–24.50)	5.00 (0.00–9.00)	3.62	−5.577	<0.001*	−2.878	0.004*
Change in ARAT	1.00 (0.00–17.00)	0.00 (0.00–4.00)	3.65	−7.841	<0.001*	−3.265	0.001*

Notes: Outcome measures presented as median (IQR); overall alpha is 0.025 for both noninferiority and superiority testing; *test on outcome difference within the given noninferiority margins or have superiority (P ≤ 0.05/3 = 0.0167); ^aMann–Whitney U or Wilcoxon Rank-Sum Location Difference Test for Non-Inferiority; ^bMann–Whitney U-Test for Two Independent Samples.

Abbreviations: IQR, interquartile range; MAS, Motor Assessment Scale; FMA, Fugl-Meyer Assessment; ARAT, Action Research Arm Test.

Figure 2 Treatment difference and non-inferiority margin. (A) Non-inferiority test for the modified intention-to-treat dataset, n = 209. (B) Non-inferiority test for the per-protocol dataset, n = 200.

Notes: Data are means (symbols) and 95% CIs (error bars) for the primary outcome difference (T-C) between nurse-led (the test group, T) and therapist-led (the control group, C) rehabilitation after seven days of treatment. The dotted lines represent the non-inferiority margins (δ).

Abbreviations: MAS, Motor Assessment Scale, δ = −6.94; FMA, Fugl-Meyer Assessment, δ = −12; ARAT, Action Research Arm Test, δ = −10.

Table 3 Median (IQR) Secondary Outcomes Scores for Each Group, and Results of GEE Analysis (PP Analysis, n = 200; Experimental Group n = 105, Control Group n = 95)

Outcome Measure	Baseline (t0)		7 Days (t1)		4 Weeks (t2)		12 Weeks (t3)		Treatment ^˄		Time Effect ^˄		Treatment× Time Effect ^˄
	Experimental Group	Control Group	Experimental Group	Control Group	Experimental Group	Control Group	Experimental Group	Control Group	Wald Chi-Square	P value	Wald Chi-Square	P value	Wald Chi-Square	P value
MBI	31.00 (20.00–50.00)	28.00 (20.00 −56.00)	52.00 (25.50 −77.50)	39.00 (23.00 −68.00)	75.00 (51.50–97.00)	68.00 (42.00 −87.00)	90.00 (71.50 −100.00)	81.00 (60.00 −98.00)	1.362	0.243	945.421	<0.001*	16.319	0.001*
NIHSS	6.00 (4.00 −9.00)	6.00 (3.00 −10.00)	5.00 (2.00–6.50)	4.00 (2.00–9.00)	2.00 (0.00–4.00)	2.00 (1.00 −4.00)	0.00 (0.00 −1.00)	1.00 (0.00 −2.00)	0.421	0.516	507.837	<0.001*	6.732	0.081
mRS	4.00 (4.00 −4.00)	4.00 (4.00 −4.00)	4.00 (3.00–4.00)	4.00 (3.00–4.00)	3.00 (3.00–4.00)	3.00 (3.00 −4.00)	2.00 (1.00–3.00)	3.00 (2.00 −3.00)	0.716	0.397	272.803	<0.001*	5.176	0.159

Notes: ^˄Results of Generalized estimating equation (GEE) analysis for group by time effect across all timepoints; *P < 0.05/3 = 0.0167.

Abbreviations: IQR, interquartile range; MBI, modified Barthel index; NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale.