Efficacy and safety of Qufushengji powder in patients with diabetic foot ulcers: study protocol for a parallel randomized controlled trial

Guo-Dong Qi; Wei Qi; Hua Wen; Kai-Qin Shen

doi:10.4103/2542-3975.300615

RESEARCH ARTICLE

Year : 2020 | Volume : 5 | Issue : 3 | Page : 37-41

Efficacy and safety of Qufushengji powder in patients with diabetic foot ulcers: study protocol for a parallel randomized controlled trial

Guo-Dong Qi, Wei Qi, Hua Wen, Kai-Qin Shen
Department of Orthopedics, Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, Chongqing, China

Date of Web Publication

19-Nov-2020

Correspondence Address:
Wei Qi
Department of Orthopedics, Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, Chongqing
China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2542-3975.300615

Abstract

Background and objective: Qufushengji powder is a classical external medicine in Chongqing Orthopaedic Hospital of Traditional Chinese Medicine for surgical ulcer. This trial is designed to demonstrate the safety and efficacy of Qufushengji powder for treatment of diabetic foot ulcers.
Participants and methods: This is a parallel randomized controlled trial, which will be conducted at Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, China. The included patients with moderate to severe diabetic foot ulcers will be randomly divided into control group and intervention group. Patients in the control and intervention groups will be sterilely bandaged with Kangfuxin solution and applied gauze strips of Qufushengji powder based on conventional therapy. In the study execution time of each stage, patient recruitment began in June 2020. The analysis of primary outcome measure will be completed in July 2021, and the study will be finished in May 2022. The protocol was approved by the Ethics Committee for Research Involving Human Subjects from Chongqing Orthopedics Hospital of Traditional Chinese Medicine on May 24, 2019 (approval No. 2019-17).
Outcome measures: Ulcer healing rate after 12 weeks of treatment is primary outcome measure. Secondary outcome measures include relief of local foot symptoms, functional recovery and adverse events.
Discussion: Results of this trial will provide preliminary evidence for the use of Qufushengji powder in the clinical treatment of diabetic foot ulcers.
Trial registration: This trial was registered in the Chinese Clinical Trial Registry on April 25, 2020 (registration number: ChiCTR2000032315).

Keywords: diabetic foot ulcers; efficacy; external prescription; Qufushengji powder; randomized controlled trial; safety; traditional Chinese medicine

How to cite this article:
Qi GD, Qi W, Wen H, Shen KQ. Efficacy and safety of Qufushengji powder in patients with diabetic foot ulcers: study protocol for a parallel randomized controlled trial. Clin Trials Degener Dis 2020;5:37-41

How to cite this URL:
Qi GD, Qi W, Wen H, Shen KQ. Efficacy and safety of Qufushengji powder in patients with diabetic foot ulcers: study protocol for a parallel randomized controlled trial. Clin Trials Degener Dis [serial online] 2020 [cited 2023 Jun 1];5:37-41. Available from: https://www.clinicaltdd.com/text.asp?2020/5/3/37/300615

Introduction

Diabetic foot ulcers (DFU) is the infection, ulcer formation and (or) deep tissue destruction of lower limbs in diabetic patients due to the combination of neuropathy and various degrees of vasculopathy. At present, the conventional treatment is the basic treatment of diabetes combined with wound dressing after decompression and the using of antibiotics.^[1] The latest epidemiological survey shows that there are about 451 million diabetes patients in the world, and up to 25% of them will develop DFU.^[2] More seriously, the 5-year mortality rate of DFU patients increased to 60% after lower limb amputation.^[3] As early as 2012, Wang et al.^[4] conducted a statistical analysis on the hospitalization information of DFU amputees, and the results showed that the average length of hospital stay was 33 days, and the total cost of hospitalization was 26,138 yuan. Another study in 2016 showed that the cost of DFU patients was about twice as much as that of non-DFU patients.^[5] Therefore, DFU has attracted much clinical attention due to its great harm, high cost, high disability and fatality rate, and has become a hot spot research in relevant disciplines. In western medicine, there are mainly advanced and effective treatment options such as autologous platelet-rich gel,^[6] negative-pressure wound therapy,^[7] hyperbaric oxygen treatment,^[8] photodynamic therapy,^[9] recombinant proteins and growth factors,^[10] and vascular intervention.^[11] Western medicine can achieve certain efficacy, but there are still some problems, the most prominent of which may be non-universality and high consumption. A retrospective clinical study combined with sociology showed that patient demographics or neighborhood socioeconomic disadvantage could influence healing rate of DFU.^[12] Considered our national conditions, the latest DFU multidisciplinary guidelines in China has pointed the important role of traditional Chinese medicine (TCM).^[13] Therefore, it is particularly important to find effective and safe treatment options with universality and low cost.

TCM has accumulated rich experience of internal and external treatment for chronic ulcer, sinus fistula and gangrene, which has achieved fruitful research results. An authoritative study has shown that the TCM external treatment has obvious curative effect on diabetic foot, and there is no potential safety hazard.^[14] In terms of drug selection, the main method is removing decay in the early stage, and generating muscle in the later stage. Jia^[15] excavated and counted data, and the result showed that the mainly compounds and classification of TCM external prescription are blood-activating and stasis-removing drugs, heat-clearing and detoxifying drugs and myogenic drugs. Qufushengji powder, unique TCM external prescription of Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, has more than 60 years of clinical history in the treatment of pressure ulcers, traumatic ulcers, varicose ulcers, gouty ulcers, bone tuberculosis and osteomyelitis-induced ulcers, sinus tracts and other symptoms, which has outstanding reputation in western China. In recent years, with the increase of DFU, the application of Qufushengji powder in this kind of disease also increases. Based on the current situation of high incidence and difficult treatment of DFU, we evaluated the clinical safety and efficacy of Qufushengji powder that has the advantages about definite curative effect, short course of treatment and low cost. This trial will provide scientific evidence for the clinical application of the prescription, thus providing a new choice of the external treatment for DFU.

Methods/Design

Design

An open-label parallel, randomized controlled trial will be carried out in Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, China. This trial was approved by the Ethics Committee for Research Involving Human Subjects from Chongqing Orthopedics Hospital of Traditional Chinese Medicine (approval No. 2019-17) on May 24, 2019 (Additional file 1 [Additional file 1]) and registered in the Chinese Clinical Trial Registry on April 25, 2020 (registration number: ChiCTR2000032315; http://www.chictr.org.cn). The screening and enrollment of the participants will be carried out for 1 year. After providing informed consent (Additional file 2 [Additional file 2]), the eligible participants will be randomized either to an intervention group or a control group. This study follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidance for protocol reporting (Additional file 3 [Additional file 3]). Trial flow chart is shown in [Figure 1].

Figure 1: Trial flow chart.

Click here to view

Patients

The study will be conducted in Chongqing Orthopaedic Hospital of Traditional Chinese Medicine and Nanjimen Street Community Health Service Center in Yuzhong district, Chongqing, China. Patients with moderate to severe DFU who will receive external therapy of TCM will be included in this trial. Under the assistance of a physician in charge, a clinical research associate will examine whether the patients meet the inclusion criteria and ensure that each patient provides signed informed consent prior to entry into trial.

Sample size

The formula will be used for sample size estimation n=2pq(Z_α+Z_β)^[2]/(p₁–p₂)^[2], where p₁ means healing rate in intervention group; p₂ means healing rate in control group; p indicates the mean value of p₁ and p₂; q indicates the mean value of 1–p₁ and 1–p₂; Z_α means that when α is 0.05, Z_α is 1.96; Z_β means that when β is 0.9, Z_β is 1.28. The primary outcome measure used for sample size determination will be the ulcer healing rate. Results from our previous system review showed that control group is 0.3 and intervention group is 0.7.^[16] Taking into account an additional 20% for attrition rate, the final sample size will be nearly 80 (40 patients per group).

Inclusion criteria

Age 18–75 years, sex unlimited;
Patients diagnosed with DFU, which accords with the classical Wagner grading method^[17] of grades 1–3 (Grade 0: no open lesions, but belongs to high-risk foot; Grade 1: superficial ulcer with skin penetration; Grade 2: deeper ulcer, including ulcers of joints and tendons; Grade 3: deep ulcer, abscess formation, tendon ligament tissue damage; Grade 4: local gangrene and bone destruction; Grade 5: total foot gangrene);
Patients did not use immunosuppressive agents, or those doses of immunosuppressive agents remained unchanged recently;
Sign the informed consent.

Exclusion criteria

Diabetic ketoacidosis, non-ketotic hyperosmolar coma patients;
Women in lactation and pregnancy;
Patients with a history of allergy to multiple drugs or recent allergies;
Patients with severe cardiopulmonary disease, cirrhosis, diabetic nephropathy or more, and unstable condition after active medical treatment;
Ulcers caused by malignant tumors;
Patients with psychiatric disorders and those without self-awareness and unable to express them accurately;
Participated in other new drug clinical trials in the last three months.

Withdrawal or replacement criteria

Participants can withdraw from the trial at any time for any reason;
Researchers will determine whether the trial should continue according to the participant’s condition;
If any participants withdraw from the trial, patient recruitment will continue until the required sample size is reached.

Randomization

The participants will be randomized to the intervention group or the control group using block randomization to ensure equal group sizes. An independent person will create the randomization sequence using random number table method. The block sizes will not be disclosed, to ensure concealment. Sequentially numbered, opaque, sealed envelopes will be used to conceal the randomization sequence. A nurse, who knows nothing about the research, will allocate the participants. The name of the patients will be written on the envelope before it is opened.

Blinding

In this trial, both the outcome assessors and the statistical analyst will be blinded to the randomization allocation and will not be involved in performance of the interventions. It will be impossible to blind the participants and practitioners since they will perform the interventional treatment. Unblinding will only occur once the outcome data collection is completed.

Treatment methods

Basic treatment

Patients in both groups will be given hypoglycemic drugs or insulin to control blood glucose according to their conditions. The wound secretions will be taken for bacterial culture and drug sensitivity test, and antibiotics will be used according to the results and drug treatment will be given depending on the patient’s peripheral neuropathy and vasculopathy.

Local treatment

Patients will be disinfected with iodophor cotton balls around the sore surface, and the sore surface will be cleaned of pus with normal saline. After shaving the rotten meat, the control group will be sterilely bandaged with Kangfuxin solution (STATE MEDICAL PERMITMENT GYZ53020054, 100 mL/bottle, SINOWAY Nature Pharmaceuticals, Kunming, Yunnan Province, China), once a day, for 12 consecutive weeks or until ulcers heal. In the intervention group, patients will directly receive Qufushengji powder on the necrotic wound surface. Afterwards, ointment or gauze will be applied, or the powder will be adhered to the paper twist and then inserted into the wound cavity, once a day, for 12 consecutive weeks or until ulcers heal. Preparation of Qufushengji powder: calamine, calcined gypsum, Hongshengdan, Jingdan, Huangbai, Longgu, borneol, blood depletion, catechu and other traditional Chinese medicines into powder; first, the drugs except Hongshengdan and Jingdan will be placed into the mortar for grinding, and then two above-mentioned drugs will be added to the mixture.

Outcome measures

Primary outcome

Ulcer healing rate: Percentage of participants whose ulcers have completely healed after 12 weeks of treatment.

Secondary outcomes

Secondary outcomes include relief of local foot symptoms, functional recovery and adverse events after 12 weeks of treatment using Qufushengji powder gauze strips and Kangfuxin solution.

The specific outcome indices are shown in [Table 1]. Before the experiment, we first register the patient’s information including informed consent, demographic data, disease course and medical history. Then, we conduct physical examination on the enrolled patients such as weight, heart rate, blood pressure, breathing, routine urine and urine, liver and kidney function, and electrocardiogram. Relief of local foot symptoms could be evaluated by ankle brachial index and skin temperature of affected limbs. Functional recovery could be evaluated by two scoring tables: pain score and indirect claudication score. Finally, safety evaluation is particularly important; after 12 weeks treatment, we could count the percentage of adverse reactions and specific adverse situation.

Table 1: Evaluation indices and time schedule of secondary outcomes

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Data management

Double data entry will be used to enter the data, so we can check for mismatches or out-of-range values. Access to the study data will be restricted. Every effort will be made to ensure confidentiality of any identifying information that is obtained in connection with this study. For confidentiality, a number (not participant’s name) will be assigned to the information participants given. All the papers including participant’s information will be kept in locked cabinets and will be destroyed when the study is done. All the information participants given will only be used for research, and will only be seen by the researcher.

Statistical analysis

Numerical data such as the incidence of adverse events and ulcer healing rate will be compared using a chi-square test. Measurement data including ankle brachial index, skin temperature of affected limbs, pain score, and indirect claudication score will be compared using paired t-test. A level of P < 0.05 is considered statistically significant. All statistical data will be processed by professional statisticians using SPSS 23.0 software (IBM, Armonk, NY, USA).

Data monitoring

The data monitoring committee has not been formed for this study because of the short duration of follow-up. The research team will trace the progress of this study, and will carry out an interim analysis. Two physicians from Chongqing Orthopaedic Hospital of Traditional Chinese Medicine will be responsible for auditing the entire process of the study, particularly data collection and analysis.

Ethics and dissemination

This research project was approved by Ethics Committee for Research Involving Human Subjects from Chongqing Orthopaedic Hospital of Traditional Chinese Medicine on May 24, 2019 (approval No. 2019-17). This trial will be conducted in accordance with the Declaration of Helsinki. All the patients will provide written informed consent. The findings of this study will be submitted to an open-access peer-reviewed journal. A full study report will be sent to Chongqing Health Care Committee, China.

Discussion

Previous studies have shown that various types of TCM external prescription could treat DFU, such as Kangfuxin liquid,^[18] Compound Huangbai liquid,^[19],[20] Yinghuang powder,^[21] and Badushenji powder.^[22] Therefore, based on exact curative effects of TCM external prescription and the classical external medicine Qufushengji powder in Chongqing Orthopaedic Hospital of Traditional Chinese Medicine for other surgical ulcer, this trail is designed to demonstrate the safety and efficacy for DFU treatment. This is the prospective randomized controlled trial to provide the 12-week follow-up results of changes in DFU patients receiving Qufushengji powder intervention or Kangfuxin liquid.

We expect that the ulcer healing rate will be improved and no adverse events occur in the intervention group compared with the control group. The results of this study will provide a new external TCM prescription for DFU, which means more universal and lower cost than other treatment.

Trial Status

Patient recruitment began in June 2020. Analysis of primary outcome measure will be completed in July 2021, and the study will be finished in May 2022. We are recruiting participants at the time of submission.

Additional files

Additional file 1: Ethical Approval Documentation (Chinese).

Additional file 2: Model consent form (Chinese).

Additional file 3: SPIRIT checklist.

Author contributions

All authors contributed towards concept, design, literature search, and critically revising the manuscript for important intellectual content. All authors gave final approval for publication.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Financial support

This study was supported by the Chongqing Science and Health Joint Traditional Chinese Medicine Research Project of China, No. 2019ZY023292 (to KQS).

Institutional review board statement

This study protocol was approved by Ethics Committee for Research Involving Human Subjects from Chongqing Orthopaedic Hospital of Traditional Chinese Medicine on May 24, 2019 (approval No. 2019-17) and will be performed in accordance with the Declaration of Helsinki.

Declaration of patient consent

The authors certify that they will obtain all appropriate patient consent forms. In the form the patients will give their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity.

Reporting statement

This study follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidance for protocol reporting.

Biostatistics statement

The statistical methods of this study were reviewed by the biostatistician of Chongqing Orthopaedic Hospital of Traditional Chinese Medicine in China.

Copyright license agreement

The Copyright License Agreement has been signed by all authors before publication.

Data sharing statement

Anonymized individual data will be available immediately after study publication upon request from those who wish to access the data for 3 years. Personal results will also be available to participants upon request. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Funding: This study was supported by the Chongqing Science and Health Joint Traditional Chinese Medicine Research Project of China, No.

2019ZY023292 (to KQS).

C-Editor: Zhao M; S-Editor: Li CH; L-Editors: Qiu Y, Wang L; T-Editor: Jia Y

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