Study design

The present study was conducted in patients who were treated for acute gouty arthritis at Tongling Traditional Chinese Medicine Hospital from January 2018 to December 2019. It was an open-labeled, randomized and controlled clinical trial. All patients were divided into two groups using the random number table method: control group, received diclofenac sodium double-release enteric capsules for treatment; treatment group, received the external use of Qingluo San combined with diclofenac sodium double-release enteric capsules for treatment. The present study was approved by the Ethics Committee of Tongling Traditional Chinese Medicine Hospital. The enrolled patients provided a signed informed consent.

Diagnostic criteria

The diagnosis of Western medicine for all the enrolled cases was referred to the diagnostic criteria for primary gouty arthritis in the 2016 China Gout Diagnosis and Treatment Guidelines [5]. Gout was classified according to 2015 ACR/EULAR gout classification standard. The diagnostic criteria for the dampness–heat syndrome in the Diagnostic Efficacy Criteria for Chinese Medical Evidence [6] and the Guidelines for Clinical Research on New Chinese Medicines (for Trial Implementation) [7] issued by the State Administration of Traditional Chinese Medicine in 2017 were mainly used in the diagnosis of the TCM syndrome. The manifestations for dampness–heat accumulation syndrome were, as follows: the small joints of the lower extremities were suddenly red, swollen and painful, refusing to be pressed with localized burning by touching and relief when cooled. The patient was accompanied by fever and thirst, restlessness and yellow urine. The tongue was red with a yellowish greasy coating. The pulse was fast and slippery.

Inclusion criteria

Patients diagnosed according to “Diagnostic criteria” section: patients within 20–70 years old; patients with no treatment before admission, and were hospitalized within 72 h after disease onset; The patients and their families had informed consent, patients with high compliance, and provided a signed informed consent for the treatment.

Exclusion criteria

Patients with severe liver and kidney diseases, cardiovascular and cerebrovascular diseases, respiratory diseases, and blood and endocrine diseases; patients with active gastrointestinal diseases; pregnant and lactating female patients; patients allergic to any of the drugs in the protocol.

Therapeutic methods

The enrolled patients with gouty arthritis were divided into the treatment and control groups, according to a random number table, and both groups were given same basic non-pharmacological treatment, which mainly included the following: lifestyle modification, elevation of the affected limb, and low purine diet; prohibition of alcohol consumption (including beer, etc.); drinking > 2000 ml of water daily; avoiding strenuous exercise or exposure to cold, etc. In the control group, 75 mg of diclofenac sodium double-release enteric capsules were administered orally, twice daily (Tamler, Germany; import drug registration number: H20140548). In the treatment group, based on the treatment in the control group, Qingluo San was externally added to the target joints, and the drug comprised the following: Sophora Flavescens Radix (9 g), Huangboon (9 g), Green Wind Vine (9 g), Rhizoma Dioscoreae Tokoro (10 g), Fructus forsythiae (9 g), Rhubarb (9 g), Corydalis Rhizoma (9 g), and Scorpion (5 g); one dose daily. The external use of Chinese herbal medicine: the powdered Chinese herbal medicine was mixed with the adjuvants (70% black vinegar + 30% honey) to make the paste. Then, the paste was applied to the painful joints, with a thickness of approximately 4 mm (the scope of external application should exceed the scope of the lesion; if skin ulcer was present, the external application should be avoided). Gauze and external application of an elastic bandage was adopted for fixation. The external application was conducted for 6 h each time, once a day, for 7 days, as a course of treatment. 7 days was a course of treatment. At 0, 1, 3, 5 and 7 days before and after treatment, it was observed and compared between both groups changes of the visual analogue scale (VAS) scores, joint tenderness, joint swelling, joint activity function and TCM syndrome scores, uric acid (UA), C-reactive protein (CRP) and ESR. After the acute phase of gout, patients were started treatment with uric acid lowering in the study.

Observation indicatorsPrimary observation indicators

The degree of pain of patients on treatment day 0, 1, 3, 5 and 7 was recorded using the VAS score (0–10 points): 0 point represented no pain and 10 points represented severe pain. The pain recording of the target joint was conducted by the patient, based on self-perception. The target joint was defined as the joint with the most severe pain, as reported by the patient at the time of enrollment.

Secondary observation indicators

The score for swelling and tenderness of the joint: on treatment day 0 and 7, the swelling and tenderness of the target joint in the patient were scored by the physician. The degree of joint swelling was scored using a 4-point scale: 0 = no swelling, 1 = palpable swelling, 2 = visible swelling, and 3 = swelling beyond the scope of the joint. The joint tenderness was scored using a 4-point scale: 0 = no tenderness, 1 = patient complained of tenderness, 2 = patient complained of tenderness and cowering, and 3 = patient complained of tenderness and avoidance.

The score for joint mobility function: no limitation to joint mobility = 0 point; limited mobility, but still able to perform normal activities = 1 point; significant limitation of mobility, and unable to perform general activities, but able to take care of themself = 2 points; felt pain during an activity, bedridden, and unable to take care of themself = 3 points.

The evaluation for total therapeutic efficacy, based on the criteria for determining the efficacy of Chinese medical syndrome in the Guidelines for Clinical Research on New Chinese Medicines: clinical cure: the disappearance or basic disappearance of TCM clinical symptoms and signs, and ≥ 95% reduction in the total score for the syndrome; significant effect: significant improvement in TCM clinical symptoms and signs after treatment, and ≥ 70% reduction in the score for the syndrome; effective: clinical symptoms and signs of TCM symptoms improved after treatment, with ≥ 30% reduction in the score for the syndrome; ineffective: no significant improvement in clinical symptoms and signs after treatment, or even presented with aggravation, with less than 30% reduction in the score for the syndrome. These effects were evaluated on the 7th day after treatment.

Observation of the efficacy of the TCM syndrome: the symptoms of joint swelling, joint pain, joint redness and heat, mobility function of the joint, fever, thirst and drinking, and yellow urine were scored before and after treatment, and the degrees were expressed according to the scoring method.

Laboratory examinations: the differences in the concentration of UA, CRP and ESR in the blood of patients in these two groups were evaluated before and after treatment.

Safety evaluation

The adverse reactions that occurred during the treatment, including gastrointestinal reactions, gastrointestinal hemorrhage, cardiovascular accidents, hemolysis, skin pruritus, redness and swelling, were recorded.

Statistic analysis

The SPSS 22.0 software was adopted for the statistical analysis of the data. The measurement data were expressed as mean ± standard deviation. Paired t-test was used for the self-control comparison before and after treatment, and unpaired t-test was used for the comparison of two groups of data. If the data do not conform to the normal distribution, the nonparametric test is used. One-way ANOVA was used for multiple comparisons, and SNK t-test was used for multiple comparisons. X2-test was used for countable data, and rank-sum test was used for rank data. p < 0.05 was considered statistically significant.