Effectiveness and Safety of Pharmacopuncture Therapy Compared to Standard Physical Therapy in Patients with Chronic Knee Pain: A Pilot Study for a Pragmatic Randomized Controlled Trial
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Inclusion and Exclusion Criteria
2.3. Interventions
2.3.1. Control Group: Standard Physical Therapy (PT)
2.3.2. Experimental Group: PPT
2.4. Outcomes
2.4.1. Primary Outcome: NRS Score
2.4.2. Secondary Outcomes
Visual Analog Scale (VAS) Score
Range of Motion (ROM) of the Knee
Korean Western Ontario and McMaster (K-WOMAC) Score
Patient Global Impression of Change Score
Short Form-12 Health Survey (SF-12) Version 2 Score
Five-Level EuroQol 5-Dimension (EQ-5D-5L) Score
Feasibility-Related Outcomes
Drug Consumption
Adverse Events
2.5. Sample Size Calculation
2.6. Recruitment
2.7. Randomization
2.8. Blinding
2.9. Data Collection and Management
2.10. Statistical Analysis
3. Results
3.1. Participant Flow
3.2. Baseline Characteristics
3.3. Treatment
3.4. Primary and Secondary Outcomes
3.5. Survival Analysis
3.6. Feasibility-Related Outcomes
3.7. Adverse Events
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
OA | osteoarthritis |
TENS | transcutaneous electrical nerve stimulation |
ICT | interferential current therapy |
KM | Korean medicine |
PPT | pharmacopuncture therapy |
RCTs | randomized controlled trials |
NRS | numeric rating scale |
PT | physical therapy |
KMDs | KM doctors |
VAS | visual analog scale |
ROM | range of motion |
K-WOMAC | Korean Western Ontario and McMaster |
SF-12 | Short Form-12 Health Survey |
HRQoL | health-related quality of life |
EQ-5D-5L | five-level EuroQol 5 dimensions |
AEs | adverse events |
ADLs | activities of daily living |
CRF | case report form |
ITT | Intention to treat |
PP | per protocol |
LMM | linear mixed model |
ANCOVA | analysis of covariance |
AUC | area under the curve |
LOCF | last observation carried forward |
CI | confidence interval |
PASS | patient-acceptable symptom state |
MCID | minimal clinically important difference |
MMP | matrix metalloproteinase |
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Total | PT Group | PPT Group | p-Value | |
---|---|---|---|---|
N = 39 | n = 19 | n = 20 | ||
Sex | ||||
Male | 17 (43.6) | 9 (47.4) | 8 (40.0) | 0.888 |
Female | 22 (56.4) | 10 (52.6) | 12 (60.0) | |
Age, years | ||||
Mean ± SD | 43.92 ± 15.26 | 45.05 ± 16.34 | 42.85 ± 14.50 | 0.658 |
<30 | 10 (25.6) | 6 (31.6) | 4 (20.0) | 0.288 |
30–39 | 9 (23.1) | 3 (15.8) | 6 (30.0) | |
40–49 | 3 (7.7) | - | 3 (15.0) | |
50–59 | 8 (20.5) | 4 (21.1) | 4 (20.0) | |
≥60 | 9 (23.1) | 6 (31.6) | 3 (15.0) | |
BMI, kg/m2 | ||||
Mean ± SD | 22.24 ± 3.69 | 22.47 ± 3.68 | 22.02 ± 3.78 | 0.705 |
<25 | 30 (76.9) | 13 (68.4) | 17 (85.0) | 0.273 |
≥25 | 9 (23.1) | 6 (31.6) | 3 (15.0) | |
Knee radiograph findings | ||||
normal | 34 (87.2) | 16 (84.2) | 18 (90.0) | 0.661 |
NCS | 5 (12.8) | 3 (15.8) | 2 (10.0) | |
Pain location | ||||
Lt. knee | 18 (46.2) | 9 (47.4) | 9 (45.0) | 1.000 |
Rt. knee | 21 (53.8) | 10 (52.6) | 11 (55.0) | |
Symptom severity | ||||
Mild (not uncomfortable) | - | - | - | 0.431 |
Moderate (uncomfortable but manageable) | 22 (56.4) | 9 (47.4) | 13 (65.0) | |
Severe (serious but untreated) | 17 (43.6) | 10 (52.6) | 7 (35.0) | |
Severe (serious and requires treatment) | - | - | - | |
Medication history | ||||
Yes | 22 (56.4) | 11 (57.9) | 11 (55.0) | 1.000 |
No | 17 (43.6) | 8 (42.1) | 9 (45.0) |
Week 1-1 | Week 2-1 | Week 3-1 | Week 4 | Week 6 | ||
---|---|---|---|---|---|---|
NRS score | PPT group | 5.87 (5.62–6.12) | 5.16 (4.64–5.67) | 3.89 (3.38–4.39) | 3.15 (2.64–3.66) | 3.15 (2.64–3.66) |
PT group | 5.45 (4.96–5.95) | 5.05 (4.56–5.55) | 5.20 (4.71–5.70) | 5.20 (4.71–5.70) | ||
Difference | — | −0.29 (−1.01 to 0.42) | −1.17 (−1.88 to −0.46) | −2.05 (−2.76 to −1.34) | −2.05 (−2.76 to −1.34) | |
p-value | — | 0.417 | 0.002 ** | <0.001 *** | <0.001 *** | |
VAS score | PPT group | 59.18 (56.77–61.59) | 51.40 (45.72–57.09) | 38.74 (33.16–44.32) | 30.63 (25.05–36.21) | 32.17 (25.98 to 38.35) |
PT group | 54.97 (49.51–60.42) | 50.67 (45.21–56.12) | 52.22 (46.76–57.67) | 50.92 (44.93 to 56.91) | ||
Difference | — | −3.56 (−11.48 to 4.35) | −11.93 (−19.77 to −4.09) | −21.58 (−29.42 to −13.74) | −18.75 (−27.39 to −10.11) | |
p-value | — | 0.373 | 0.003 ** | <0.001 *** | <0.001 *** | |
K-WOMAC score | PPT group | 59.31 (53.69–64.92) | — | — | 43.02 (36.96–49.07) | 41.49 (35.43–47.55) |
PT group | — | — | 56.18 (50.28–62.09) | 54.93 (49.03–60.84) | ||
Difference | — | — | — | −13.17 (−21.67 to −4.67) | −13.45 (−21.95 to −4.94) | |
p-value | — | — | — | 0.003 ** | 0.003 ** | |
PCS score | PPT group | 39.62 (37.67–41.57) | — | — | 43.52 (40.84–46.20) | 44.35 (41.67–47.03) |
PT group | — | — | 42.03 (39.41–44.64) | 42.00 (39.39–44.62) | ||
Difference | — | — | — | 1.49 (−2.26 to 5.25) | 2.35 (−1.41 to 6.10) | |
p-value | — | — | — | 0.429 | 0.216 | |
MCS score | PPT group | 51.48 (48.60–54.36) | — | — | 53.27 (50.28–56.26) | 54.85 (51.86–57.84) |
PT group | — | — | 51.89 (48.97–54.80) | 51.01 (48.09–53.92) | ||
Difference | — | — | — | 1.39 (−2.84 to 5.61) | 3.85 (−0.38 to 8.07) | |
p-value | — | — | — | 0.515 | 0.074 | |
EQ-5D-5L score | PPT group | 0.73 (0.69–0.76) | — | — | 0.81 (0.77–0.85) | 0.81 (0.77–0.85) |
PT group | — | — | 0.78 (0.74–0.82) | 0.75 (0.72–0.79) | ||
Difference | — | — | — | 0.03 (−0.02 to 0.08) | 0.06 (0.01–0.11) | |
p-value | — | — | — | 0.286 | 0.030 * |
Group | Adverse Event (LLT) | Severity | Causality |
---|---|---|---|
PT | Bruise | Moderate | Certain |
PT | Bruise | Moderate | Certain |
PT | Paresthesia | Mild | Possible |
PT | Bruise | Mild | Certain |
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© 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jeong, M.I.; Lim, J.K.; Kim, Y.J.; Jeon, Y.S.; Kim, S.; Kim, C.Y.; Park, Y.-C.; Kim, E.-J.; Hong, Y.; Nam, D.; et al. Effectiveness and Safety of Pharmacopuncture Therapy Compared to Standard Physical Therapy in Patients with Chronic Knee Pain: A Pilot Study for a Pragmatic Randomized Controlled Trial. Medicina 2025, 61, 1106. https://doi.org/10.3390/medicina61061106
Jeong MI, Lim JK, Kim YJ, Jeon YS, Kim S, Kim CY, Park Y-C, Kim E-J, Hong Y, Nam D, et al. Effectiveness and Safety of Pharmacopuncture Therapy Compared to Standard Physical Therapy in Patients with Chronic Knee Pain: A Pilot Study for a Pragmatic Randomized Controlled Trial. Medicina. 2025; 61(6):1106. https://doi.org/10.3390/medicina61061106
Chicago/Turabian StyleJeong, Myung In, Jun Kyu Lim, Yong Jun Kim, Yu Sun Jeon, Suna Kim, Chang Youn Kim, Yeon-Cheol Park, Eun-Jung Kim, Yejin Hong, Dongwoo Nam, and et al. 2025. "Effectiveness and Safety of Pharmacopuncture Therapy Compared to Standard Physical Therapy in Patients with Chronic Knee Pain: A Pilot Study for a Pragmatic Randomized Controlled Trial" Medicina 61, no. 6: 1106. https://doi.org/10.3390/medicina61061106
APA StyleJeong, M. I., Lim, J. K., Kim, Y. J., Jeon, Y. S., Kim, S., Kim, C. Y., Park, Y.-C., Kim, E.-J., Hong, Y., Nam, D., Lee, Y. J., Kim, D., & Ha, I.-H. (2025). Effectiveness and Safety of Pharmacopuncture Therapy Compared to Standard Physical Therapy in Patients with Chronic Knee Pain: A Pilot Study for a Pragmatic Randomized Controlled Trial. Medicina, 61(6), 1106. https://doi.org/10.3390/medicina61061106