Search results

Our search strategy identified 217 records, one of which was in an English language database. After removing 51 duplicates, 166 papers were included initially, 153 of which were subsequently excluded because they did not meet the inclusion criteria (not an RCT, n = 41; animal studies, n = 37; wrong intervention, n = 23; and wrong disease, n = 52). Of the 13 potentially eligible studies, six were excluded from further assessment; in one of these, the comparator was a Chinese herbal medicine that lacked sufficient evidence of effect, two studies assessed the wrong intervention, the exclusion criteria were unclear in two studies, and the remaining study had unclear inclusion and exclusion criteria. The missing information in one study could not be obtained and it is awaiting assessment. Therefore, our review includes six studies (607 Chinese participants; Fig. 1).

Fig. 1

Summary of the search results in a flow diagram

Included studiesParticipants

Six studies [40,41,42,43,44,45] were included comprising 607 adults with gout. The trial populations were small, ranging from 64 to 180 Chinese participants (average: 101.17 participants). All of the studies were conducted in China. The ratio of male to female participants in five of the trials was 345/180 [40, 41, 43,44,45]. Participant ages ranged from 30 to 87 years. The disease duration was not reported in two of the studies [40, 42]. In total, 607 adults with gout were included in six studies, and all of the participants were from China.

Interventions

The primary intervention was oral administration of the Chinese patent medicine Tongfengding capsule. The therapy duration ranged from 7 days to 12 weeks. The follow-up duration was 6 months in two studies [41, 45], three studies mentioned follow-up but did not specify the duration [42,43,44], and the remaining study did not mention follow-up [40]. All six studies compared Tongfengding capsule plus conventional treatment versus conventional treatment alone. NSAIDs, urate-lowering drugs, and symptomatic treatment were the main conventional treatments for gout in adults. The medication used in these studies including NSAIDs (diclofenac sodium dual release enteric-coated capsules [44] and diclofenac sodium enteric-coated sustained release capsules + indomethacin [45]), xanthine oxidase inhibitor (allopurinol [40] and Febuxostat tablets [43]), xanthine oxidase inhibitor (Benzbromarone capsules) + indomethacin [41], and colchicine + xanthine oxidase inhibitor (allopurinol) [42].

Outcomes

The total effective rate was reported in four studies [41,42,43,44], BUA concentration was reported in four studies [40, 41, 43, 45], CRP and ESR were reported in one study [40], Il-6, Il-8, and TNF-α levels were reported in two studies [40, 43], 24-h UTP was reported in one study [40]; SCr and BUN were reported in one study [43]; the relapse rate and adverse effects were reported in two studies [41, 45], and the withdrawal rate was reported in one study [42]. However, none of the studies reported all-cause mortality, economic index, or TCM tongue and pulse assessment (tongue coating and pulse). The characteristics of the included studies are shown in Table 2.

Table 2 Characteristics of the included studiesRisk of bias in the included studies

The methodological quality of each study, including the randomization sequence, allocation concealment, blinding (blinding of the personnel and participants and blinding of the outcome assessment), incomplete outcome data, selective outcome reporting, and other bias is shown in Figs. 2 and 3.

Fig. 2Fig. 3

Methodology quality summary

Randomization and allocation concealment

All six included studies [40,41,42,43,44,45] reported that the patients were randomized; however, only four provided sequencing details [40,41,42, 45], all of which used a random number table to assign groups [40,41,42, 45]. We conducted telephone interviews with the authors of the remaining two studies and found that one used a computer-generated random sampling table [44] and the other used a random number [43]. Although none of the six studies [40,41,42,43,44,45] reported their allocation concealment methods, we concluded that the concealment procedures were sufficient because the investigators were not actively involved in treatment, and the physicians treating the participants were unaware of the study outcome parameters.

Blinding

Three studies [43,44,45] reported using double blinding (neither the participants nor investigators were aware of the drug allocation) and single blinding (participants were not aware of the outcome assessment), but did not describe their procedures. We interviewed the original authors by telephone to clarify their blinding procedures and concluded that the studies had low risks of performance and detection biases. In contrast, the risks of performance and detection biases in the three studies [40,41,42] that did not mentioned blinding procedures are unclear.

Incomplete outcome data

The outcome data were clearly reported in the included studies [40,41,42,43,44,45], which showed no withdrawals, dropouts, and/or loss to follow-up. However, the methods used to handle missing data (i.e., per-protocol analysis or intention-to-treat) were not described.

Selective reporting

Although none of the six included studies [40,41,42,43,44,45] provided detailed evidence of selective reporting, the published papers included all of the expected outcomes, including those that were pre-specified. Funnel plot was not performed due to small sample size.

Other potential sources of bias

The participant demographic characteristics were comparable among the six included studies. Four studies mentioned that their institutional ethics committees approved the protocol and that written informed consent was obtained from each participant [40,41,42, 45]. We confirmed ethics committee approval and written informed consent in the remaining two studies [43, 44] in telephone interviews with the authors.

Excluded studies

We excluded six studies from our review. Of these, one was excluded because the comparator was a Chinese herbal medicine that did not have sufficient evidence of efficacy; two were excluded because they used the wrong intervention; one was excluded because the inclusion and exclusion criteria were not clear; and the remaining two studies were excluded due to unclear exclusion criteria.

Studies awaiting classification

One potentially eligible study is awaiting assessment because the information provided is not adequate to determine whether it meets the inclusion criteria for our review, and we have been unable to contact the original authors directly.

Effects of interventionsPrimary outcomeTotal effective rate

Four studies [41,42,43,44] reported that Tongfengding capsules plus conventional treatment significantly increased total effective rate when compared to conventional treatment [Fig. 4; Analysis 1.1; RR 1.21, 95% CI 1.11–1.33; I2 = 0%].

Fig. 4

(Analysis 1.1): Comparison. Chinese patent medicine Tong-Feng-Ding-Jiao-Nang capsules plus conventional treatment versus conventional treatment. Outcome 1: Total effective rate

Secondary outcomesBUA

A significant decrease in BUA was observed with Tongfengding capsules plus conventional treatment versus conventional treatment [Fig. 5; Analysis 1.2; MD − 66.05 µm/L, 95% CI − 81.26 to − 50.84; I2 = 90%].

Fig. 5

(Analysis 1.2): Chinese patent medicine Tongfengding capsules plus conventional treatment versus conventional treatment. Outcome 2: BUA. BUA: blood uric acid

Three subgroup studies [40, 41, 43] reported that Tongfengding capsules plus urate-lowering drugs combined with relieve pain drugs significantly decreased BUA when compared to urate-lowering drugs combined with relieve pain drugs [Fig. 5; Analysis 1.2.1; MD − 80.35 µm/L, 95% CI − 83.04 to − 77.66; I2 = 0%].

One subgroup study [45] reported that Tongfengding capsules plus NSAIDs significantly decreased BUA when compared to NSAIDs [Fig. 5; Analysis 1.2.2; MD − 28.95 µm/L, 95% CI − 47.19 to − 10.71].

Kidney function (24-h UTP, SCr, and BUN)

One study [40] reported that Tongfengding capsules plus conventional treatment (allopurinol) significantly decreased 24-h UTP and BUN when compared to conventional treatment [Fig. 6; Analysis 1.3.1; MD − 0.83 g/24 h, 95% CI − 0.96 to − 0.70] and [Fig. 6; Analysis 1.3.3; MD − 0.90 mmol/L, 95% CI − 1.60 to − 0.20], respectively. In contrast, the study [40] showed that Tongfengding capsules plus conventional treatment did not significantly decrease SCr when compared against conventional treatment [Fig. 6; Analysis 1.3.2; MD − 4.02 µm/L, 95% CI − 8.18 to 0.14].

Fig. 6

(Analysis 1.3): Chinese patent medicine Tongfengding capsules plus conventional treatment versus conventional treatment. Outcome 3: Kidney function (24-h UTP, SCr, and BUN). 24-h UTP: 24-h urinary total protein; SCr: serum creatinine; BUN: blood urea nitrogen

Inflammatory factor (Il-6, Il-8, and TNF-α)

Two studies [40, 43] reported that Tongfengding capsules plus conventional treatment (allopurinol [40] and Febuxostat [43]) significantly decreased Il-6, Il-8, and TNF-α when compared to conventional treatment [Fig. 7; Analysis 1.4.1; MD − 6.99 ng/L, 95% CI − 13.22 to − 0.75; I2 = 96%], [Fig. 7; Analysis 1.4.2; MD − 12.17 ng/L, 95% CI − 18.07 to − 6.27; I2 = 93%], and [Fig. 7; Analysis 1.4.3; MD − 8.50 ng/L, 95% CI − 15.50 to − 1.51; I2 = 97%], respectively.

Fig. 7

(Analysis 1.4): Chinese patent medicine Tongfengding capsules plus conventional treatment versus conventional treatment. Outcome 4: Inflammatory factor (IL-6, IL-8, and TNF-α). IL: interleukin, TNF-α: tumor necrosis factor-alpha

Related indicators (CRP and ESR)

One study [