This is a prospective randomized controlled superiority clinical trial to evaluate the efficacy and safety of fire needle acupuncture compared to filiform needle acupuncture for knee osteoarthritis. One-hundred participants with knee osteoarthritis will be randomly allocated to the fire needle and filiform groups at a 1:1 ratio. The schedule of enrollment, interventions and assessments is summarized in Table 1, and the flow diagram of the study procedure is presented in Figure 1. Patients’ recruiting is from November 2020. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1).
Trial participants with knee osteoarthritis will be recruited from outpatient clinics at the Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Meanwhile, information flyers introducing the details of the trial will be posted at the outpatient clinics for greater exposure.
This study consists of two phases including: (i). a baseline phase (Week 0), (ii). a 6-week treatment phase (Week 1 to Week 6).
Once potential participants show interest in this trial, they will be invited to attend an eligibility assessment in which their eligibility will be assessed by trial investigators; thereafter, eligible participants will be enrolled and randomly assigned to either the fire needle group or the filiform needle group and given a 6-week treatment.
Participants who meet all of the following requirements will be considered for inclusion: (1) diagnosed as having osteoarthritis according to American College of Rheumatology Clinical Classification Criteria for Osteoarthritis of the knee (2) graded II-III of Kellgren-Lawrence Radiographic Classification , (3) aged between 30-75 years old, (4) VAS score of knee joint pain is over 4 out of 10, (5) received no medication or relevant treatment in the past two weeks, (6) provided written informed consent.
Patients will be excluded if they have (1)non-primary knee osteoarthritis (e.g. secondary knee osteoarthritis, inflammatory or other rheumatic diseases), (2) history of trauma, surgery, meniscus or ligament damage, or severe joint deformity on knee joint, (3) serious cardiovascular, cerebrovascular, lung, liver, spleen, kidney or hematopoietic system diseases, tumors, hemorrhagic diseases, or mental diseases, (4) difficulty in cooperating with the examination and receiving quantitative evaluation, (5) female participants who are pregnant or lactating, (6) cicatricial or hypersensitive to acupuncture treatment.
Randomization and allocation concealment
The randomization will be performed by the Research Centre of Clinical Epidemiology, Peking University Third Hospital. A block randomization method will be used to generate the random allocation sequence; predetermined computer-generalized randomization opaque sealed envelopes will be used to ensure the allocation concealment. The opaque sealed envelopes, with the participant’s screening order printed outside and randomly assigned group printed inside, will be numbered consecutively, and connected into a strain. Researchers will enroll the eligible participants after screening, then separate and open each envelope from the strain in the sequence corresponding to the participant’s screening order, and assign the eligible participant into either the fire needle group or filiform needle group.
The statistician who generates the randomly assigned sequence is not the same person as the researcher who decides whether the subject is qualified. People who generates or saves the randomly assigned sequence cannot participate in the trial process.
Outcome assessors and personnel involved in data collection and data analysis will be blinded to participants’ group allocation throughout the entire trial. The acupuncturist and participants cannot be blinded due to the nature of the intervention, but they will be informed not to communicate with outcome assessors regarding treatment procedures and responses.
All participants will receive the allocated intervention twice a week for 6 weeks. All participants will go through a standardized interview and be provided with details of the study. The acupuncturist who perform treatments for both groups are registered with the Ministry of Health of the People’s Republic of China as Chinese medicine practitioners and have more than 20 years clinical experience. Before the trial begins, all acupuncturists will receive special training regarding the purpose and standard procedure of the trial, treatment strategies, and quality control. The treatment details will be fully documented in accordance with the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) and good clinical practice guidelines.
Fire needle group
Acupoints including ashi point (local pain point), bilateral ST34 (Liangqiu), bilateral SP10 (Xuehai), bilateral ST35 (Dubi), bilateral EX-LE4 (Neixiyan), and bilateral GB34 (Yanglingquan) will be acupunctured, using a tungsten manganese alloy fine fire needle with a size of 0.5mm x 25mm. All locations of the acupoints will be identified according to The Location of Acupoints -- the national standard of the People's Republic of China (GB12346-90). Operating method (Figure 2): participants will be treated in the supine position with the knee-bent. First, the acupoints will be identified by nail scratches and then sterilized. Then the needle will be rapidly stabbed into place and pulled out, about 0.5cm deep, three times at each point, when the tip and the middle part of the needle body have been burned red by an alcohol lamp. After pulling out the needle, pressure will be briefly applied to the needle hole with a sterilized cotton ball to avoid bleeding, and the patients will be asked to keep these areas clean and to avoid infection.
Filiform needle group
The same acupoints will be selected for acupuncture treatment by the filiform needle (the name of the brand: Andi), with a size of 0.3×40mm. According to the patient’s somatotype, vertically stick the needle in 15-25mm at the points. Operating method (Figure 3): mild reinforcing-attenuating, evenly lifting, inserting, and twisting, then retaining the needle for 20 minutes.
The efficacy of the treated patients will be evaluated before treatment and 6 weeks after intervention. The main efficacy indicator is the WOMAC questionnaire for knee pain, stiffness, and function. The secondary efficacy outcomes are VAS for generalized pain and SF-12 for quality of life. The collected information and data will be maintained confidentially
WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)
WOMAC is a standardized questionnaire used to evaluate the condition of subjects with osteoarthritis of the knee and hip, which assesses the three dimensions of pain, stiffness and functional limitation with 24 questions. The score range for each question is 0 to 4. The total score of WOMAC is on a scale of 0 to 96, and higher scores indicate more severe symptoms.
VAS (Visual Analogue Scale)
The VAS score is used to assess knee joint pain. It ranges from 0 to 10, and a higher score means more severe pain. The efficacy evaluation mainly refers to the Outcome Measures in Rheumatological Clinical Trials formulated by the Osteoarthritis Research Society International (OMERACT-OARSI), i.e., the pain has been highly improved when the score decreases ≥50% and the absolute value declines ≥2; Pain has been improved to some extent when the score decreases ≥20% and the absolute value declines ≥1, which is the minimum variation for clinical significance.
SF-12 (12-item Short Form Health Survey)
The SF-12 scale consists of two parts: physical component sub scale and mental component sub scale. Converted by a specific formula, the total score is on a scale of 0 to 800, and higher scores represent better health. The conversion formula is presented in Figure 4. The conversion formula is presented in Figure 4.
Adverse reactions related to acupuncture include pain, fainting, bleeding, hematoma, infection, nerve injury, aggravation of an underlying disease, severe skin allergy, stuck needle (i.e., the therapist feels sluggish and astringent under the needle, and has difficulty twisting, lifting and inserting the needle, and the patient feels pain during the acupuncture process), a bent needle, a broken needle, etc. The classification of adverse events refers to adverse drug reactions: level 1: Safe, without any adverse reactions. Level 2: Relatively safe. If there are adverse reactions, the participants can be treated sequentially without any treatment of the complication. Level 3: There are safety problems and moderate adverse reactions. The participants can continue to receive treatment after the reactions have been taken care. Level 4: the treatment was terminated due to the adverse reaction. Constitutional or local symptoms, signs and adverse reactions will be dynamically observed, and recorded, which will be used for comprehensive analysis.
For adverse reactions related to the trial, the therapists will give symptomatic treatment such as hemostasis, disinfection, and anti-inflammatory according to the specific situation.
The study will be regularly monitored by the Data Management and Monitoring Committee of the Good Clinical Practice Department of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. The Data Management and Monitoring Committee are independent of the trial researchers and has no competing interests. The Data Management and Monitoring Committee will monitor the overall quality and integrity of the data, examine original case report forms, interview the researchers, verify the record of adverse events, and confirm that the study conforms to the principles of this protocol.
Sample size calculation
In a previous study, the WOMAC score after treating by fire needle was 52.83±20.85 and 59.92±23.80 days in the filiform needle group. Based on the relevant literature we have consulted, the minimal clinically important difference (MCID) of WOMAC scores was set at 6.7. It is set that the inspection level is 0.05 (α=0.05, two sided), and the power of the test is 0.2 (β=0.2), using a 1;1 ratio, i.e. the sample size of fire needle group (n1) =the one of filiform needle group =40. Considering the loss rate of 20% or less, a sample size of 50 per group and a total number of 100 participants will be recruited during the entire study accordingly.
Using the statistical software of SPSS 20.0, p<0.05 for two-sided test will be regarded as the standard to judge the significance of the difference. The measurement data will be expressed as mean ± standard deviation (±s). If the precondition of a parametric test is satisfied, t-test will be chosen. For non-parametric data, a Wilcoxon rank sum test will be used. The counting data will be expressed as frequency (or rate), which is calculated by a chi-square test or Fisher's exact test.
The results of the study will be statistically analyzed according to the principle of Intention-To-Treat (ITT) and Per-Protocol population (PP). In ITT, all enrolled participants who have treated at least once will be analyzed. In PP, all participants who meet the study criteria, have completed the observation, have good compliance, do not use prohibited drugs during the study, and complete the study contents will be analyzed. Finally, comparison of the consistency of results between ITT and PP will be conducted. The multiple imputation method will be used to process the missing data for the primary outcome.
Ethics and dissemination
This study will adhere to the principles of the Declaration of Helsinki(2008), Measures for the Ethical Review of Biomedical Research Involving Humans(2007) issued by the ministry of health, and Administrative Regulations on the Ethical Review of TCM clinical research(2010) issued by State Administration of Traditional Chinese Medicine of the People's Republic of China, and it has been approved by the Research Ethics Committee of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University on 8 June 2018 (reference 2018SB-066). The study has been registered with Chinese Clinical Trial Registry (ChiCTR) on 18 November 2018 and the registration number is ChiCTR1800019579. The results will be disseminated through publications in open source scientific peer reviewed journals, presentations in scientific conferences, or a master’s thesis. The identifying images or other personal or clinical details of participants that compromise anonymity will not be published.