Study design
This study is a multi-center and single-blind, randomized, sham-controlled clinical trial. It aims to compare and analyze the one-time analgesic effect between intervention group and sham-controlled group (Fig 1, Table 1) for acute pain in patients with dementia. This protocol was designed on the basis of SPIRIT guidelines and the Consolidated Standards of Reporting Trials (CONSORT) statement [16, 17]. The Ningxia Medical University Ethics Committee has given its give official approval for the study protocol, which has been registered at Chinese Clinical Trial Registry (No.: ChiCTR2100047932). Each patient will be given a detailed explanation by the researcher including the purpose, benefits and potential risks of the study. Moreover, they can withdraw from the study at any time. And this will not affect medical services other than research. Subsequently, the qualified recruits signed informed consent entering the study will receive APP or shamed APP treatment by a investigator, a master candidate in nursing science with APP professional training.
Study setting
This randomized controlled trial is being conducted at three nursing homes in Yinchuan, China. These three aged care institutions are the largest and public in the region, with approximately 2,000 permanent residents.
Patients
All 206 patients met inclusion and exclusion criteria are being recruited from the three nursing homes. Recruitment is expected to take place from December 2020 to December 2021. The recruits with informed consent before entering research will be randomly allocated to an intervention or a sham-controlled group in a 1:1 ratio. Furthermore, it is feasible to have enough patients to meet the target sample size in three nursing homes. Inclusion criteria include: (1) aged 60 or above with speaking Chinese; (2) dementia was diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (DMS-V) criteria [18]; (3) diagnosis of mild or moderate dementia based on the Montreal Cognitive Assessment (MoCA) [19]; (4) acute pain and a score of pain ≥4 based on the Face Pain Scale Revised (FPS-R); (5) their healthy condition permits the use of a multifunctional pulse oxygen monitor; (6) understanding the meaning of the FPS-R; (7) volunteering to participate in the study and signing the informed consent (caregivers, patients, and/or family members). Exclusion criteria are as follows: (1) moderate or severe dementia; (2) medical contraindication for ear acupressure (inflammation, ulcers, frostbite in the ear); (3) history of allergy to adhesive tape and alcohol; (4) critically ill patients who have no response to the effectiveness and safety of new treatments (serious heart, brain, liver, kidney, or hematopoietic system diseases);(5) patients who received drugs for pain management.
Interventions
The intervention group will be planned to receive auricular-plaster therapy, with one piece of Semen Vaccariae® (about 2 mm in diameter, Taicheng Technology and Development Co., LTD, Shanghai, China) attaching to the center of a piece of medical adhesive tape (6 mm × 6 mm). This study initially selected four active acupoints including shenmen (TF4), subcortex (AT4), adrenal (TG2P) and two auricular points corresponding to pain sites based on Nogier auricular point diagram for managing pain [20]. A researcher will bring required items to the participants’ bedside and assist them in taking position that is easy to operate. Subsequently, the researcher holds the helix with left hand and identifies sensitive points by virtue of an ear probe with the right. The medical adhesive tapes with Semen Vaccariae® will be pasted on the selected auricular points with forceps by the researcher after checking and sterilizing the skin of the patients’ ears using 75% alcohol. Then, each auricular point will be pressed gently 1~2 times with lasting 1 minute each times. There is no time interval during the operation unless adverse reactions occur or until finishing the procedure. The pressure should be moderate and enough within individual’s endurance (the subject feels swelling pain, numb, and warm sensation). After the whole intervention, these tapes will be removed. The control group will be treated with sham APP (at sham points stimulation), its procedures are described in the intervention group. However, the subject simply experiences the warm sensation on their ears.
Randomization and blinding
Sequence numbers of each patient will be generated by a computer-produced random list, which is performed by an independent, blinded statistical expert from Ningxia Medical University. The randomization list will only be kept by the researcher who performed the intervention. To ensure the concealment of data distribution and minimize selection bias, other researches (the manager who is responsible for the study protocol, data collectors, etc.) and caregivers (nurses and unlicensed assistive personnel) are blinded to the randomized controlled trial lists. Furthermore, no recruiters who signed informed consent forms know whether they are receiving real APP or sham APP treatment.
Measurement
Each patient’s demographic data (age, sex, nationality, educational background, marital status, occupation before retirement, personal income per month, history of taking medicine, chronic case history) will be recorded by a self-designed questionnaire. Other information including physiological parameters (heart rate, blood pressure and oxygen saturation), sore spot, pain score, adverse effects, the use of analgesics in the intervention, satisfaction of caregivers as well as acceptance of patients will be more rigorously documented. The MoCA is made to identify the severity of dementia among the patient. And locality of the pain will be shown clearly according to the Brief Pain Inventory (BPI-C) [21]. The FPS-R with great reliability and validity will be elected to assess pain intensity, and three physiological parameters are monitored with electronic sphygmomanometer (OMRON, HEM-7120) and Fingertip Oximeter (PC-60B). The data required for the study include pain score, noninvasive monitoring of blood pressure, heart rate collected at baseline (before performing the intervention, T0), at 5 min during performing the intervention (T1) and at 5 min after the intervention finished (T2) as well as digital monitoring of oxygen saturation. Any adverse effects observed of APP treatment should be well planned to handle and detailed recorded. even if there is no reports of it. Simultaneously, the use of analgesics in the intervention also will be carefully recorded to enhance analysis the safety and analgesic effect of APP. Satisfaction from caregivers will be surveyed via a five-point satisfaction scale (5, very satisfied; 4, satisfied; 3, uncertain; 2, dissatisfied; 1, very dissatisfied) at T2 [22]. However, acceptance of patients will be measured by just asking them if they’d like to accept the APP treatment once again.
Outcome measurement
Primary outcome measure
The level pain relief at T1, and T2 will be considered as the primary outcome. It is accurately recorded by a researcher in charge of recording on the basis of the FPS-R.
Secondary outcomes measure
The secondary endpoints are consisted of physiological parameters, any adverse reactions observed, satisfaction from caregivers, acceptance of participants, additional use of analgesics during the intervention. The duration of the intervention will also be included in the secondary outcomes.
Sample size estimation
After obtaining the ethical approval of our study protocol, a preliminary experiment with a sample size of 30 was conducted in Nursing Home, Yinchuan on January 2020. The results of the pilot study indicated that in the FPS-R score of the control group and the intervention group was 5.97 ± 1.81 and 4.79 ± 1.96, respectively. We have consulted a statistician from the School of Medical Statistics and Epidemiology in Ningxia Medical University, who finished the randomization list of the recruits. With type-1 error rate of 0.05 (α= 0.05, two-tail) and a 90% power (β= 0.10), the sample size of the study scheme was calculated by the statistical expert, which was 86 patients in each group. According to our study design and considering the particularity of this research subject (they are less likely to complete the entire experiment), we assume a 20% drop-out rate. The total sample size 206 cases (per group was 103 cases) are required to reduce the underpower of the study.
Management and safety monitoring
Prior to the study, research team members will receive a training program, which will cover research design, procedure, evaluation of outcome measures, randomization, data collection and data monitoring. For example, data recorders will be trained how to collect and manage data to ensure the objectivity, quality and safety of data as far as possible. Participants information will be protected confidentiality before, during, and after the trial. With the consent of the project leader, only members of the research team have access to the collected information for a reasonable reason. It should be also noted that the information of patients who withdrawn will not be included in the final analysis, and other researchers will investigate what led them to withdraw from the trial. Data Management and Safety Monitoring Committee is not necessary due to the APP treatment was the least risky. But regular monitoring and auditing data will be required. Finally, an independent statistician is responsible for the evaluation and processing of the final data.
Data statistical analysis
On the basis of the intention-to-treat (ITT) principle, SPSS version 22.0 (Chicago, IL, USA) will be recommended to run the data statistical analysis on both real APP group and sham APP group. Information on all patients in the random list should be included in the final analysis. If data is missing, the missing data imputation should be used to analyze the validity of the statistical analysis. Statistical description of categorical variables (the population demographic data) will be mainly presented by the relative number (rate, proportion and ratio). The continuous variables (repeated measurement data of three physiological parameters ) will be compared by analysis of variance (ANOVA) or the Kruskal-Wallis test (or Chi-squared tests) for two groups. Other categorical variables (data on satisfaction from caregiver, acceptance from patient and additional use of analgesics) will be described by the nonparametric test (Wilcoxon’s rank sum test). A two-sided P values <0.05 will be considered to be statistical significance.