Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial

Background Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. Objective Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. Methods A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. Results Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. Conclusions The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. Trial Registration ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619 International Registered Report Identifier (IRRID) DERR1-10.2196/54352

If more than two aspects are affected, three adjunct acupoints will be chosen from those for the relevant syndromes The selection of the three customized acupoints will be based on the experience of the acupuncturist.Therefore, the number of needles used is eight (unilateral).Ie ST34, ST36, ST32, ST40 and EX-LE2 will be used for pain at the stomach meridian.GB31, GB36, GB34, GB39 and GB41 will be used for pain at the gallbladder meridian.BL39, BL40, BL57 and BL60 will be used for pain at the bladder meridian.LR7, SP9, SP10, KI10, SP4, SP6, LR3 and KI3 will be used for pain at the three-yin meridians of the foot.Integrating Acupuncture With Exercise-Based Physical (EPT) Therapy for KOA:…  On the posteromedial aspect of the knee, just lateral to the semitendinosus tendon, in the popliteal crease.The Knee Osteoarthritis TCM Evaluation Form is designed on the basis of KOOS-12 Knee Survey.In addition to the questions from KOOS-12 (highlighted in grey), questions according to TCM syndrome differentiation of KOA in Singapore are included.The final score will be combined to evaluate the outcome.

Study
The acupoints used in the protocols of these several RCTs were considered in our intervention =

Figure S2 .
Figure S2.Meridian Differentiation in KOA and acupoints selected According to the Meridian Theory, all six meridians of the foot travel through the knees.Figures adapted from 'A Manual of Acupuncture' by Deadman P, Baker K, Al-Khafaji M, 2007.Table 1.Meridians of the foot Lateral position Medial position Posterior position Anterior position The Gallbladder meridian of Foot-Shaoyang The Spleen meridian of Foot-Taiyin, The Liver meridian of Foot-Jueyin, The Kidney meridian of Foot-shaoyin

Figure S3 .
Figure S3.Progression and Severity of Knee OA defined in the TCM Clinical Guidelines published in China 21 These guidelines were subsequently used to help in the development of the TCM evaluation forms (Figure S4 an S5) .

Figure S6 .
Figure S6.Symptoms, Tongue Appearance and Pulse Readings according to Syndrome differentiation of Knee Osteoarthritis (KOA) in Singapore 48Table 1. Syndrome differentiation of Knee Osteoarthritis (KOA) in Singapore Syndrome Primary symptoms Secondary symptoms Tongue & Pulse

Table 2 .
Selected Acupoints for the Intervention Group On the tibial aspect of the leg, in the depression between the inferior border of the medial condyle of the tibia and the medial border of the tibia.

Table 1 :
Progression of KOA and Symptoms Observed at Each Stage, as Defined in TCM Clinical Guidelines

Table 2 :
Symptoms of Varying Severity of KOA (Mild, Moderate and Severe), as Defined in TCM Clinical Guidelines

Knee Osteoarthritis Visual Analog Scale & Range of Motion Evaluation Form
Kindly evaluate the symptoms and indicate the score for each itemThe following questions concern your physical function.By this we mean your ability to move around and to look after yourself.For each of the following activities please indicate the degree of difficulty you have experienced in the last week due to your knee.

Table 1 .
Syndrome differentiation of Knee Osteoarthritis (KOA) in Singapore Dull pain or pulling pain at fixed location.Pain aggravated during night.Lassitude Knee swelling, darken or dark red colour around the knee, Unfavourable knee flexion & extension.Aversion to cold and preferred warm.Frequent urination Pale, fat tongue with bruising spots or pale & dull tongue.Thin, white coating.Sunken, fine pulse or fine, sluggish pulse 48 Cai H. xin jia po xi guan gu xing guan jie yan (KOA) zhong yi zheng xing fen bu yan jiu [TCM syndrome distribution study of Knee Osteoarthritis in Singapore].