Fire needle plus cupping for acute herpes zoster: Study protocol for a randomised controlled trial

doi:10.21203/rs.2.9440/v4

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Study protocol

Fire needle plus cupping for acute herpes zoster: Study protocol for a randomised controlled trial

https://doi.org/10.21203/rs.2.9440/v4

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published 06 Aug, 2020

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Background

Acute herpes zoster (AHZ) is a common skin disease caused by invasion of the varicella-zoster virus into the ganglia and skin, and the severe pain is the most complaint, which can seriously disturb the normal life of patients. Fire needle plus cupping is a special acupuncture treatment, which is widely used to treat AHZ for its better analgesic effect in China although it has not been fully verified by rigorous randomized controlled trial (RCT).

Methods/ Design To test the effect, a three-arm randomized parallel controlled trial protocol has been designed. 105 AHZ patients suffering pain will be randomly divided into three groups in an equal proportion. The interventions are fire needle plus cupping (FC) in group A , famciclovir plus gabapentin (FG) in group B and fire needle plus cupping plus famciclovir (FCF) in Group C. The length for the trial is set for a week time frame. Precisely speaking, the A group (FC ) is to carry out 1 treatment per day for the total of 7 treatment sessions within 1 week period, On the other hand, the B group (FG) will take drugs orally three times a day within the trial 1 week . Meanwhile, with its combination element, the C group (FCF) is due to undertake both treatments and drugs as prescribed for A and B groups within the trial week. As an intra-trial arrangement, analgesics medication will be carefully administered for temporary pain release if the sudden intolerable pain appeared. For the primary outcome, this study is due to apply visual analogue scale to identify pain intensity relief. As the secondary outcomes are concerned, this study is aiming to focus on the issues related to changes in substance P and beta-endorphin concentrations in peripheral plasma, as well as those issues of analgesic needs, side effects, symptoms and physical signs including pain classification, local itching, burning sensation, fever, local lymphadenopathy, skin lesion area, blisters, herpes clusters, vesicular traits, ulcers, and pimples; and all these are taking into account for evaluation. For the final stage, the participants are due to be followed up for postherpetic neuralgia.

Discussion: The results of this trial aim to provide sufficient evidence on FC treatment over both FG and FCF treatments. It will then give a credible alternative treatment to cut down acute pain and to cure AHZ infection.

Trial registration: The registration number is ChiCTR1800015372. Registered on 28 March 2018.

Anesthesiology & Pain Medicine

Infectious Diseases

Fire needle plus cupping

Acupuncture

Acute herpes zoster

Randomized controlled trial

Protocol

Herpes zoster (HZ), is a skin infection disease caused by reactivation of varicella zoster virus which is latent in the sensory ganglia, with typical feature is that it causes herpes along the sensory nerve in the corresponding segment, accompanied by severe neuralgia, and a serious impact on the quality of life of patients ^[1]. Pain symptom is the most common in early stage of disease and many of them without visible herpes appearance. As such it is easy to be misdiagnosed for other diseases, for example, misdiagnosis of cervical spondylosis or lumbar disc herniation when pain symptom occurs on the neck and shoulders. Another misdiagnosed case example is associated with heart-related disease if the HZ symptom appeared on the left chest. All these misdiagnosed cases are not rare of ordinary occurrences^[1]. HZ can occur at any age, but elderly population seems to be most commonly affected. Epidemiological study shows that the incidence, complications, hospitalization rate and average cost of HZ in China are climbing rapidly with the age increasing^[2]. The cumulative incidence with HZ infection is 22.6/1000 among people aged over 50 years old, and this rate climbs up to 3.34 times more among the age group of over 80 years old ^[2].

The conventional drug therapies for HZ infection can be seen in two phases. Those in acute phase are mainly antiviral, nutritional nerve, and analgesic^[3] types of drugs. The antiviral drugs are mainly oral famciclovir and valacyclovir. The nutritional nerve drug is mainly mecobalamin, and the pain relief drugs are mainly paracetamol tramadol, dezocine, morphine and gabapentin. However, upon an individual's health condition, glucocorticoid drugs may be administered orally or intravenously. As in the sequelae phase, treatment drugs are mainly analgesic and antianxiety, and the oral drugs include tricyclic antidepressants, strong opioids, gabapentin, tramadol, pregabalin, etc. In addition, the drugs such as methylprednisolone and triamcinolone acetonide can be used as nerve-blocking therapy. All of these above-mentioned conventional drug schemes yield potential side effects, and it is especially for patients with renal insufficiency or immune system diseases as for these patients the above-mentioned schemes are difficult to implement^[3]. Furthermore, the cumulative medical cost is high for such treatments on this disease, and patients are not fully satisfied and even with the curative effect. With all these downsides of conventional drug therapies, it is said to believe complementary and alternative medicine such as acupuncture may give better results with less side effects and reduce medical costs to treat HZ infection. ^[3-4].

Although HZ infection is not a lifelong disease, patients still suffer deeply with excruciating pain, yet it requires faster, economical, and effective treatments to relieve pain and shorter treatment courses. Acupuncture treatment has a positive therapeutic effect on pathological neuralgia, and a number of analgesic mechanisms have also been identified^[5-9]. Fire needle and cupping are both traditional methods in acupuncture treatment, and its history can be rooted in many ancient Chinese ancient literatures. The fire needle treatment is to use the alcohol lamp to burn the tip point of the special needle, and then the needle will be pierced into and pull out the meridian or acupoint quickly -- these two steps can yield both ordinary acupuncture and warming effects. When the needle operation is completed, the third step of cupping therapy is implemented immediately. This combining three steps therapy is widely used in the treatment of acute pain symptoms of HZ infection in Chinese hospitals nation-wide, however the test of efficacy of this treatment has not been performed under rigorous RCTs^[10-12].

Evidently by several decades of current and ancient traditional Chinese medicine (TCM) practitioners as well as literatures of TCM,the treatment of fire needle plus cupping(FC) has a positive effect to promote qi and activate blood circulation , which then in term could increase the nutrition around the lesion and promotes tissue regeneration, and resulting in natural wound healing. Ancient TCM practitioners also found that the heat provided by fire needles can promote microcirculation in the lesion area through the regulation of cutaneous nerves, and it is particularly beneficial to the absorption of inflammation and metabolites^[13]. Furthermore, the high temperature of fire needles can generate an effect that directly kills the microorganisms and achieves anti-inflammatory outcomes ^[14]. Therefore, this trial is aiming along the same line as Ancient TCM practitioners and to further provide the fact results in order to validate the analgesic effect on acute herpes zoster (AHZ) treated by trial grup A (FC).

Objective

The main purpose of this trial is to gather evidence for the designed treatment in group A (FC) and investigate the effect of designed treatment on relieve the acute pain phase in AHZ. Another objective would also analyse the correlation between the concentration of substance P and β-endorphin (â-Ep) in peripheral plasma and changes in pain intensity by FC intervention.

Study design

As shown in Figure 1, this study is a three-arm open randomized controlled trial consisting of three groups. The interventions are fire needle plus cupping (FC) in group A, famciclovir plus gabapentin (FG) in group B and fire needle plus cupping plus famciclovir (FCF) in Group C. After a randomization selection process, Group A and Group C received a total of 7 treatment sessions of fire needles cupping therapy within 1 week trial time. The administration of gabapentin depends on the needs of the patient of Group B. In addition, if the acute pain cannot be endured, patients will give the temporary analgesics medicine.

The visual analogue scale (VAS) scores, symptoms, and physical scores are due to obtain for pre- and post-treatment periods. The concentrations of SP and β-Ep in peripheral plasma also will be detected, and demand for temporary analgesics and side effects of the patients are recorded daily. As the final stage, after 6 months, the participants are due to be followed up for postherpetic neuralgia, 6 months after treatment (Figure 2).

Participants and recruitment

This study aims to recruit 105 patients by postering public posters in both local dermatology and acupuncture clinics and the website of the Sixth Affiliated Hospital of Kunming Medical University. When potential participants have read the poster they can contact the dermatologists Zuohui Liang and Xiuhong Liu through the contact phone number indicated on the poster. Potential patients then got enrolled and signed the consent form if they meet the inclusion criteria by the assessment of dermatologists. Meanwhile, a randomized grouping technique has been conducted. While preparing and unpacking all relevant information, Shihua Li is responsible for such matter. The first formal trial recruitment began in November 2018. The assistant researcher will assess and record the baseline status of the participants (Table 3).

In order to achieve an adequate enrolment rate, we have developed two attractive offerings to gather patients’ attention as well as publicize recruitment notices. They are: First, all treatment and cost under this trial are free of charge for selected patients r. Second, if participants with postherpetic neuralgia six months later, they are entitled for another 10 sessions free comprehensive acupuncture treatments t.

Randomisation and allocation concealment

(1) Block setting: 105 participants are numbered 1-105 according to the time of participation, the block length is 6, and 16 blocks are set.

(2) Obtaining random numbers: Start with any two-digit number in the random number table, and take 105 numbers to the right.

(3) Grouping: 6 random numbers of each block are sorted from small to large, sorts 1 and 2 are group A, sorts 3 and 4 are group B, and sorts 5 and 6 are group C.

(4) Random group concealment: The grouping conditions of participants are packed into 105 envelopes, and all the envelopes are numbered in order and sealed. To ensure the randomization process, the serial number will be printed on the outside of the opaque envelope and the assignment of the group will be sealed on the inside of the envelope.

Shihua Li, an otolaryngologist at the Sixth Affiliated Hospital of Kunming Medical University, is responsible for the above matters and she doesn’t get involved in the process of treatment and the data collection of this study.

The envelope will be opened according to the patient’s serial number, and the dermatologists will be responsible to inform patients by phone on their random number and assignment.

Blinding

In order to eliminate operational shortcoming of blinding issues since treatment for FC and FCF group could not be performed blind, we will, instead, first conceal information related to randomized grouping and the results association with the grouping of subjects, and then we seek to provide sensory tests (outcome evaluators), data inspectors and statistical analysts who are not aware of the detail grouping and treatment of subjects as a blind.

Participating physicians

Participating physicians in the trial are doctors selected from the departments of dermatology and acupuncture and moxibustion at the Sixth Affiliated Hospital of Kunming Medical University. As acupuncturists are responsible for the treatment of FC and FCF, the all highly qualified and have received a master’s degree in acupuncture and moxibustion as well as have undergone training in unified Standardized operation plan.

Patient and public involvement

Patients and/or public were not involved in the design of this study.

Participants

Inclusion criteria

18 to 60 years old, with no gender difference;
Skin rash and clustered blister in asymmetrical skin area;
Precursor symptoms such as general discomfort and fatigue before rash;
Nervous pain in the affected area, skin hypersensitivity,
The rash is distributed along the innervated area;
Unilateral, not exceeding the midline of the body;
Pain intensity as assessed by VAS (0-100 mm) of 50 mm ≤ pain intensity ≤80 mm；

Exclusion criteria

Insulin-dependent diabetes mellitus or other diseases that affect peripheral sensitivity (e.g., polyneuropathy, chronic pain syndrome);
Bleeding tendency (e.g., taking anticoagulants, coagulation dysfunction, thrombocytopenia, etc.);
Pregnancy or lactation;
Surgery within the past 3 months;
Diseases affecting quality of life (e.g., cancer, paralysis);
Mental illness (e.g., depression, schizophrenia, dementia) or severe heart/lung/kidney disease;
Exposure to fire needle, cupping, painkillers, or other complementary and alternative treatments for this disease prior to treatment;
Contraindications for famciclovir, gabapentin, mecobalamin, paracetamol, tramadol, dextrozine, fire needles, and cupping.

Dropout

Case dropout

(1) Subjects experienced other comorbidities, complications, or special physiological changes during the trial. They are classified as not suitable to continue the trial.

(2) During the trial, serious adverse events and important adverse events occur in the subjects, so that they are not suitable to continue the trial, and investigators decide to withdraw.

(3) Subjects have poor compliance. Medication compliance is calculated using the tablet counting method. Medication compliance = dose taken / prescription dose × 100%, medication compliance <80% or missed fire needle plus cupping treatment ≥ 1 time is defined as poor compliance.

(4) Violation of the test plan. Subjects change or add drugs other than the study protocol, and received other treatments other than the study protocol during the trial period.

(5) The subject withdrew out by himself.

(6) Lost follow-up at the final stage.

Management of dropout cases

For dropout cases, researchers should actively take measures to complete the last laboratory test as far as possible in order to analyse its efficacy and safety. For all dropout cases, the test conclusion form and reason for dropout shall be filled in the case report form.

Intervention

Group A

This group will be treated with only FC.

Acupoints: The main points are Ashi points (lesion area), corresponding nerve segment Jiaji points, and branch ditch points (SJ6); matching points are selected according to syndrome differentiation, pattern of dampness-heat in the liver meridian with Yang Ling Quan (GB34), pattern of dampness-heat in the spleen meridian with Yin Ling Quan (SP9), and pattern of obstruction of collaterals by blood stasis with blood sea (SP10).
Appliances: Medium-sized fire needle (diameter 0.4mm), large-sized fire needle (diameter 0.65mm), glass fire cup No.1-5, medical cotton ball, alcohol lamp, lighter, iodophor, etc.
Operational methods: Routine disinfection of skin with iodophor with the order of the head, middle, and tail of herpes will be carrying out firstly. Holding 95% alcohol lamp by the left hand close to the needle, and to burn the needle in the right hand to whitening by the external flame of the fire, acupuncturist will prick the head of the herpes cluster. Then the needles will be pricked into the blisters or rashes quickly from the surface of the skin to the base of the herpes. Pricking early-onset herpes at first, for larger pustules or blood blisters (diameter ≥5cm) with a large-scale fire, acupuncturist will extrude blister fluid with disinfection cotton ball after puncture, and then cup with a suitable size of glass fire cup for 5-10 minutes. If the area of the herpes cluster is too large, more than one cup can be used. The remaining acupuncture points are treated with fire needle pricking, and each acupuncture point should be pricked three times. Finally, the skin should be sterilized with iodophor more than one times. The treatment should be performed once a day for a total of 7 days.
Skin care: After treatment, the iodophor is used to clean and disinfect the skin, and to keep the patient’s skin dry and clean during the treatment.
Courseof treatment: The course of treatment is one week and from one to seven times. If there is no pain any more after one time of FC treatment, the course is just one time. Meanwhile, if the patient is still suffering pain, the FC will continue once a day unless the pain disappears. All the treatments will not be more than seven times no matter the pain or not.

Mechanism of fire needle cupping

Based on the theory of traditional Chinese medicine, the main causes of herpes zoster are dampness and heat, which could block the meridians and collaterals, and then led to the stagnation of blood and Qi, and finally the pain is generated. FC has a strong effect to eliminate the dampness and heat, and make the Qi and blood smooth running, and then the pain will be alleviated. Previous studies hint that FC can accelerate crusting and shedding of herpes, and also adjust the concentration of substance P in serum^[11-12].

Group B

Patients in Group B are intervened with famciclovir plus gabapentin (FG). The famciclovir hydrochloride dosage is 0.25g/time, 3 times a day according to the manufacturer’s (Livzon Pharmaceutical Factory) recommendation. The individual dose of gabapentin is 900-3600 mg per day. According to the manufacturer’s (Jiangsu Hengrui Pharmaceutical Co., Ltd.) recommendation (Table 1), the initial dose of 300 mg per day is gradually increased to 900 mg per day and then increased according to the patient’s needs, and the maximum dose is 3600 mg per day.

Table 1 demonstrates the gabapentin intake scheme used to reach the wanted therapeutic dosage.

Group C

In group C, patients will receive the treatment of FC plus famciclovir (FCF). The FC is performed as same as group A, and the usage and dosage of famciclovir hydrochloride are in line with group B.

Temporary analgesics

If the patients in the three groups who still cannot endure the pain during the treatment or after one week treatment, For all patients who have difficulties to endure pain during the trial, as an intra-trial arrangement, temporarily analgesics medicine will be given to those in need with careful observation. According to the recommendations of the World Health Organisation, all three groups are likely to receive standardized analgesic treatment as step 1: non-opioid analgesics (paracetamol 4 × 1.0g), 60mm≤ VAS≤ 50mm; step 2: moderate-strength opioids (tramadol tablets, maximum dose 600mg/d), 80mm≤ VAS≤ 70mm; step 3: moderate-strength opioids (tramadol injection, 0.1g, once a day), VAS=90mm; step 4: recommend the use of stronger opioids (dezocine injection, 5mg, once a day), VAS=100mm. Patients are forbad to use other analgesic drugs or therapies. Temporary analgesics demand will be recorded (table 2).

Adverse events

Adverse events like symptoms or diseases occurring during the trial will be recorded (table 2) and assessed at each session of intervention. There may be adverse events of abnormal gastrointestinal reactions, allergic reactions, dizziness, burns and other medical conditions. The relevance and severity of the adverse events will be assessed. Whether the participant could continue the treatment or not will be decided according to the assessments. To those who suffer harm as a result of the treatment will be compensated in accordance with relevant regulations.

Follow up

To evaluate the incidence of postherpetic neuralgia symptom, a follow-up call is designed and recorded 6 months later posted after the end of the one week treatment. (table 2).

Outcomes

Primary outcome

The primary outcome has been the changes in pain intensity pre- and post-treatment (VAS 0-100 mm, where 0 = painless and 100 = maximum imaginable pain).

Secondary outcomes

First of all, pre- and post-treatment periods, the plasma of the participants are carefully collected and centrifuged and stored in a - 80℃ refrigerator. It is then the substance P and â-Epin in serum can be detected by an enzyme-linked immunosorbent assay. Quantitative scoring methods have been further applied to evaluate the symptoms and physical signs before and after treatment, including pain intensity local itching burning sensation rash colour, numbers of blisters clusters ulcers fever local lymphadenopathy rash area (Table 2).

Data management and monitoring

The study will be conducted according to common guidelines for clinical trials (Helsinki Statement, 2008 Chinese Edition, http://www.chictr.org.cn/index.aspx) and will be jointly audited by the Audit Office, Science and Technology Department and Finance Department of Kunming Medical University. Trial auditing will be twice a year since that is the frequency of meeting with the Trial Steering Group of principal investigators. Data will be uploaded to the ResMan Public Management Platform of the China Clinical Trial Registry for adequate quality and safety control. The registration number is ChiCTR1800015372. Therefore, no Data Safety Monitoring Committee is needed. The principal investigator is responsible for project oversight, will make the final decision to terminate the trial, and will have access to the final trial dataset.

Confidentiality and dissemination

The personal information of all the participants stored on computers is kept on a secure server and will always be kept confidential. All the documentations of this study will be kept in a locked and secure environment (locked office and cabinets) at the Six Affiliated Hospital of Kunming Medical University. The review will be submitted to a peer-reviewed journal prospectively to spread our findings.

Statistical methods

Sample size estimation

We will compare the difference in efficacy of the three groups. Sample size estimation is based on the method of the book of health statistics ^[15], with type I error alpha = 0.05 and type II error beta = 0.1, using the bilateral test. According to the literature, the cure rates of famciclovir and for fire needle plus cupping for HZ were 37.8% and 76.4%, respectively. It was speculated that the cure rate of famciclovir plus fire needle plus cupping was 80.0%, which was substituted into the formula:

Where P_max =0.80 and P_min =0.378. The calculated result was a sample size of 32 subjects per group. Therefore, the number of samples required for the three groups was 96. This study required a total of 105 samples adding a 9%-10% dropout rate.

Statistical analysis

The purpose of this study is to confirm whether the therapeutic effect of experimental therapy (fire needle cupping) is different from that of reference therapy (famciclovir plus gabapentin and fire needle cupping plus famciclovir). Spss20.0 statistical software will be used for data analysis. When the main efficacy indicators of individual subjects are missing, the last observation carried forward will be conducted, and the non-main efficacy indicators will not be carried forward. The mean ± standard deviation is used for statistical description of measurement data, and the frequency (constituent ratio) is used for statistical description of counting data. The baseline characteristics will be recorded as in Table 3. The group t-test (Bonferroni method) will be used to compare the measurement data between groups. All reported P values will be two-tailed with 95% confidence intervals. The value of P ≤0.05 will be considered statistically significant. PPS analysis and Fas analysis will be performed at the same time. SS analysis is used for safety evaluation.

This study is a randomized controlled clinical trial with the grouping comparison of FC, FG and FCF., To our knowledge so far, this study may be the first clinical trial study that aims to demonstrate the FC effect on AHZ infection with rigorous design and it may also be different from the reference therapy. However, it has gotten our attention that several existing Chinese literatures did report on fire needle and cupping technique to cure for HZ^{[12, 13, 14, 16]} but all of them did not take up a rigorous design trial and is lacking of sufficient evidence to proof FC treatment has positive effect on AHZ.

The key objective of this study is to test the three designed treatment groups on the analgesic effect in acute phase of AHZ disease. We will also pay great attention to the observation of the scores of skin lesions, since skin rash is also the deep concern of patients. We also want to detect variation in serum due to the fact that the substance P and â-Epin is often regarded as the analgesic mechanism. In addition, the occurrence of postherpetic neuralgia may need to be carefully observed and examined due to it’s commonly occurrence and hard to cure nature in AHZ infection. The symptom of acute pain is that the AHZ patient want to solve mostly and cannot approve to participate in an invalid treatment group.

This study is intended to design a rigorous trial protocol that will yield evidence on effective acupuncture technique. In that, this study should be closer enough to the clinical real-world research. Nevertheless, there are confounding factors associated with this designed trial that cannot be completely avoided. First, there is no separate set of sham acupuncture as a control group for FC treatment. Since the first group of FC treatment is already a combination of two types of acupuncture techniques, it is hard to implement another set of sham acupuncture. Another issue of the ethical principle will also make it difficult to perform sham acupuncture for FC treatment since conflicts in interests may happen for patients who have already suffered from severe pain and won’t be likely to accept sham acupuncture. Note that, however, the psychological effects cannot be ruled out for lack of sham acupuncture group ^{[18, 19]}. Second, the blind method is also impossible to perform under the current designed trail since it is not possible for acupuncturists and subjects to do so under the operation of FC treatment. Instead of blinding, the FG and FCF treatments have both been designed to set as the control interventions. As such, the results from FG would be good enough to give evidence of comparison and FCF is also a good way to show whether the combination of drug with FC treatment will yield a better result than the FC treatment alone. Third, as in our clinical practice, acute pain associated with AHZ infection tends to be amplified alongside with the development of the AHZ disease. It is therefore, as an intra-trial arrangement, the temporary short-acting painkillers will be permitted to all the selected patients regardless of their group divisions. Having such intr-trail, temporary and low dose pain release drugs will have no obvious effect on the results. Another limitation of this trial is the psychological factors can't be eliminated according to the present design, and the difference in immunity is relative to the recovery of HZ which may lead to differences in prognosis. Finally, according to the actual clinical situation, the drug dose, as well as the number of FC treatment interventions, has certain volatility and does not restrict sternly.

In all, this protocol will act to provide a reference of clinical methodology and may give definite evidence on the effect of FC intervention for AHZ as it is designed.

This trial protocol is version 2.1, dated 24 April 2019. This trial will be recruited on 10 October 2019, and recruitment will be completed about on 10 October 2020.

Herpes zoster: HZ; acute herpes zoster: AHZ; randomised controlled trial: RCT; β-endorphin: â-Ep; Visual analogue scale: VAS; fire needle + cupping: FC; famciclovir + gabapentin: FG; fire needle + cupping + famciclovir: FCF; traditional Chinese medicine: TCM.

Acknowledgements

We would like to acknowledge Professor Guohua Lin of Guangzhou University of Traditional Chinese Medicine, who gave some suggestion at the beginning of this study design. We would like to acknowledge Dr. Lynn Cheng, who is a special researcher at Chengdu University of Traditional Chinese Medicine, who helped us revise this English language manuscript. We would also like to acknowledge the funding support programs for agreeing to sponsor the study, and the reviewers for their helpful comments on the manuscript.

Funding

This work was supported by the Yunnan Provincial Science and Technology Department–Kunming Medical University Applied Basic Research Joint Project (No. 2017FE467 (-147)) and Yunnan Province "Ten Thousand Plan" Youth Top Talent Program (NO.: YunRen SheTong [2019] 206). The role of the funding bodies is in charge of the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. If important protocol modifications occur, the principal investigator will report to the Science and Technology Department of Kunming Medical University.

Authors’ contributions

* Correspondences are XhL ([email protected]) and TpG ([email protected]);⁺YZ and ZhL are the co-first authors of this paper. YZ and TpG conceived of the study and drafted the manuscript. YX and TpG participated in the design of the study. YX performed the sample size estimation and was responsible for the blocked randomization of patients. YL is responsible for coordination of the study. XhL, ZhL, and JjY are responsible for subject recruitment. QnX, QZ, ClL, and JZ are responsible for fire needle and cupping treatment. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study protocol has been approved by the Medical Ethics Committee of Yuxi people’s Hospital (No.: 20170730-01).Written informed consent will be obtained from each participant.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Authors' information

1.The Six Affiliated Hospital of Kunming Medical University, Yuxi 653100, China

2.School of Acupuncture-Moxibustion and Tuina and Rehabilitation, Yunnan University of Chinese Medicine, Kunming 650500, China

3.The Third People's Hospital of Yunnan Province, Kunming 650011, China

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Table 1: Gabapentin Scheme
Day Time	8:00 a.m.	14:00p.m.	22:00 p.m.
1	-	-	300 mg
2	300 mg	-	300 mg
3	300 mg	300 mg	300 mg
Increase depending on patient’s needs
4	300 mg	300 mg	600 mg
5	600 mg	300 mg	600 mg
6	600 mg	600 mg	600 mg
...
7（Maximum dose）	1200 mg	1200 mg	1200 mg

Table 2: Secondary outcomes
Symptom or sign(points)	0	1	2	3
Pain intensity	no	mild	medium, tolerable	severe, unbearable
local itching	no	mild	medium, tolerable	severe, unbearable
Burning sensation	no	mild	medium, tolerable	severe, unbearable
Rash colour	no	light red	red, no edema	red, edema
No. of blisters	no	1-10	11-15	＞26
Blisters clusters	no	1-2	3-4	4-5
Ulcer	no	epidermis	superficial ulcer	deep ulcer
Fever	no	≤38℃	≤39℃	＞39℃
Local lymphadenopathy	no	＜0.5cm	0.5-1 cm	＞1cm
Rash area reduction percentage	0	＜30%	＜60%	100%
Analgesic demand(day) 1 2 3 4 5 6 7
Paracetamol(g)
Tramadol (mg)
Tramadol injection(g)
Dezocineinjection(mg)
Side effects

Table 3. Baseline characteristics

characteristics	value
Age, mean±SD, y
Gender, n (%) male Female
Onset days, mean±SD, d
VAS score, mean±SD Quantitative score, mean±SD

Onset days are the time from the patient's onset of pain or rash to inclusion.

Quantitative score is quantitative score of symptoms and signs

Additional file 1: Ethical Approval Document. (PDF 120kb)

Additional file 2: Funding Documentation1. (PDF 145kb)

Additional file 3: Funding Documentation2. (PDF 139kb)

Additional file 4: Informed consent. (PDF 145kb)

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published 06 Aug, 2020

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Fire needle plus cupping for acute herpes zoster: Study protocol for a randomised controlled trial

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