Settings and subjects
The present study was a randomized controlled trial, conducted by the Guangzhou Hospital
of Chinese Medicine, the First Affiliated Hospital of Guangzhou University of Chinese
Medicine, and the Liwan District Hospital of Chinese Medicine. The study reporting
complied with the requirements of the CONSORT 2010 statement.[10]
Patients were randomly divided into either Arm 1, Arm 2 or the control group. The
grouping was performed by personnel from the Key Research Laboratory of Clinical Research
Methodology at the Guangdong Provincial Hospital of Chinese Medicine. SAS 9.2 was
used to complete the procedure, and for randomization. The trials were single-blind
so that the data analyst and evaluator were unaware of the groupings. Neither patients
nor the clinical doctors performing the interventions were blinded. In order to avoid
bias, individuals responsible for the evaluation of the efficacy were hired separately,
and were unaware of patient groupings. Analysts were also chosen separately and did
not participate in the clinical implementation, or the design of the project.
The trial was conducted between July 2016 and July 2017, and patients who met the
following criteria were included in the study:
(1) diagnosed with ischemic cerebrovascular disease by either CT or MRI[11]
(2) recovery period (2 weeks to 6 months after acute stroke), sequelae period (June
to December)
(3) number of strokes ≤ 3
(4) aged between 40 and 75, male or female
(5) clear cognitive faculties, stable vital signs, no obvious mental retardation,
no obvious hearing impairment, and ability to cooperate with rehabilitation training
(1) had already received other treatments that were not part of this research plan
(2) suffered from transient ischemic attack, or reversible neurological deficit (RIND)
(3) neurological deficit was not related to ischemic stroke
(4) suffering from mental disorders or other severe diseases
(5) patients with severe aphasia, sleep apnea, deafness, severe cognitive impairment,
or communication barriers
Treatment process
The standards of the study met the requirements of the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) 2010.[12] Before the trial, the research team was authorized by the Ethics Committee of the Guangzhou Chinese Medicine Hospital, the First Affiliated Hospital of Guangzhou University
of Chinese Medicine, and the Liwan District Chinese Medicine Hospital (Reference no. 2016NK001) to conduct the study. All included cases were treated with basic drugs, such as
those to improve circulation, nourish nerves, prevent platelet aggregation, and control blood pressure, blood sugar, and blood lipids. Patients also received rehabilitation
training.[11、13] Rehabilitation training followed the guidelines of the Rehabilitation Treatment Guide 2011 of Stoke in China14] and Practical Rehabilitation.[15] The members of the rehabilitation team examined the patient to determine the nature
and extent of the disorder. The rehabilitation team also held review meetings to integrate
patient care, formulate a rehabilitation plan and implement treatment. According to
the specific conditions of the patients, they were trained to sit, balance, stand,
shift their center of gravity, walk, feed themselves, change clothes, or go to the
bathroom. They also received systemic coordination training which included balancing,
practical walking, using a walking stick, and going up and down stairs.
Acupoints
The optimal acupoint scheme for this test was determined by a consensus of acupuncture
experts and previous clinical research.[16] One group’s treatment was based on an acupoint summary from ancient literature,[17-18] and the other’s was based on a summary of effective acupuncture points from a consensus
of acupuncture experts from modern RCT literature (Supplement 1). The most frequently used twelve acupoints in the ancient books and the modern RCT literature were determined by the consensus of acupuncture experts and previous clinical research. In treatment Arm 1, these included DU20 (baihui), DU26 (shuigou), PC9 (zhongchong), ST6 (jiache), ST4 (dicang), LI15 (jianyu), LI11 (quchi), LI4 (hegu), GB30 (huantiao), GB31 (fengshi), GB34 (yanglingquan) and GB39 (xuanzhong). In treatment Arm 2, they were DU20 (baihui), PC6 (neiguan), LI11 (quchi), LI10 (shousanli), SJ5 (waiguan), LI4 (hegu), GB30 (huantiao), ST36 (zusanli), GB34 (yanglingquan), SP6 (sanyinjiao), ST41 (jiexi) and LR3 (taichong). Other than PC9 and PC6, all acupoints were selected from the affected side.
Acupuncture intervention
The acupuncture treatment was performed by 16 different acupuncturists (with between
2 and 7 years’ experience) at 3 different hospitals. 7 of the acupuncturists had bachelor’s
level educations, 6 had master's degrees, and 3 had doctorates and were registered
practitioners of Chinese medicine. All researchers and acupuncturists were required
to undergo a four-day training session prior to the trial.
Appropriate positioning of the needles is crucial to obtaining good acupuncture results.
The patients in the study lay in a lateral position with the affected side facing
up, the hemiparalysis shoulder stretched forward, the shoulder joint flexed 90 degrees,
and the paraplegic upper limb on a pillow at a 100° angle to the trunk. The elbow
was straightened, with arm, wrist and fingers extended, and palm facing up. Next,
the paraplegic side of the lower extremity was placed on the pillow, revealing a step-like
shape (with hips and knees flexed). The disposable sterile acupuncture needles used
had varying specifications (0.30 x 25 mm, 0.30 x 40 mm, 0.30 x 50 mm, or 0.30 x 75
mm). Conventional disinfection with 75% alcohol was employed after acupuncture point positioning, in accordance with Standard Acupuncture and Moxibustion Positioning by WHO.[19] During the acupuncture session, patients would feel soreness, numbness, distension or heaviness around the point, or an electric shock
feeling during needling, demonstrating that needling had been effective. In order to stimulate needle sensation,
the needles were inserted flat and backwards, 25 mm into DU20, and 8-15 mm obliquely
and upward into DU26. Then, a reducing method was used for 30 s, rotating at small-amplitude
and high-frequency. The other acupoints utilized the reinforcing-reducing method 2.5
mm deep into PC9; 15-20 mm vertically into ST6, ST4, GB39, ST41 and LR3; 15-25 mm
perpendicularly into LI4, PC6, and SJ5; 25-40 mm obliquely and downward into LI15;
25-40 mm perpendicularly into LI11, GB34, GB31, LI10, ST36, and SP6; and 50-70 mm
perpendicularly into GB30. After insertion, the needles were left in situ for 30 minutes.
The course of treatment was 5 times a week, for 2 weeks. All necessary precautions
were taken to prevent, record and treat any adverse events that occurred during treatment
(e.g. fainting, broken needles).
Outcomes
The treatment effect of this trial was evaluated by three scales, at different time points (Baseline=T0, Week 1 = T1, Week 2 = T2 and Follow up = T4). The primary outcome was expressed using the National Institute of Health Stroke Scale
(NIHSS). It ranged from 0 to 40, and included 11 items: consciousness, limb movement,
eye movement, vision, facial paralysis, feeling, language, dysarthria and neglect.
It also determined improvement in neurological function among the three groups (i.e.
the lower the score, the lesser the patient’s neurological deficit). The secondary
outcomes were the Barthel Index Table (BI) and the Modified Ashworth Scale (MAS).
The BI scale is typically used to assess patient self-care ability, and if the score
is below 20, this means that the patient’s self-care ability had been seriously impaired.
A score of over 60 indicated patients had been able to care for themselves. The improvement
and difference in muscle tension within the three groups was determined by the changes
in the modified Ashworth scale, both before and after treatment—the higher the score,
the higher the patient's muscle tone. Returning to the hospital after discharge is not an easy task for patients, and only
BI data for these three observations could be obtained in a remote setting such as
a telephone conversation. Thus, only BI was measured 4 times.
Sample size
According to Yang,[20] the NIHSS score for simple stroke rehabilitation was (12.78±2.99), and the NIHSS
score for acupuncture combined with stroke rehabilitation was (16.06±4.57). Setting
α to 0.05, β to 0.1, and substituting the sample size formulae of the two groups of
means, the results showed that 30 patients were necessary for each group to complete
the trial. Considering that the two treatment groups were compared with the control
group, in order to control for type 1 error, the number of patients in each group
was increased to 30*3=90. Assuming a 10% dropout rate per group, each group was adjusted
to 100, with a total of about 300 patients.
Statistical analysis
An intention-to-treat population was surveyed before the analyses, which included
those patients undergoing baseline assessment and at least one evaluation after treatment.
The NIHSS, BI and MAS scores, along with changes over time, were compared by using repeated measures designed for the three groups. We also employed
Analysis of Variance (ANOVA) to define the among-group differences at each measure time point. A Chi-square or Fisher Exact test was used to analyze
categorical variables, including categorical baseline variables and incidence of adverse
events. Last observation carried forward (LOCF) was used in the ITT analysis to address
missing data due to attrition and shedding. Statistical significance was defined as
a two-tailed P < 0.05. Statistical analysis was performed with PASW 20.0 (IBM SPSS Inc., Armonk, New York, USA).