Page | 003 surgery with the ultimate goal to improve the patients’ quality of life.
objECtIvEs
The primary objective of this randomised controlled trial is to evaluate the long-term efficacy and safety of PLFMF on the management of CLBP and on increasing the percentage change in Numerical Rating Scale (NRS) pain at week-24 with respect to baseline score. The percentage reduction in NRS pain at week 24 will also be evaluated according to various musculoskeletal CLBP subtypes based on pain mechanism (nociceptive vs peripheral neuropathic vs central sanitisation).11–13
The secondary objectives are to evaluate the effects of PLFMF on (1) pain intensity during treatment and early after treatment completion, (2) level of disability, (3) functional levels, (4) sleep quality, (5) quality of life and (6) fatigue in patients with CLBP. The study will also investigate the long-term side effects of PLFMF.
This study will also include subgroups exploratory objectives to clarify the role of PLFMF in the manage- ment of patients diagnosed with different subtypes of musculoskeletal CLBP. To the best of our knowledge, this trial is the first randomised clinical trial to explore simultaneously the role of PLFMF in the management of patients with peripheral neuropathic, nociceptive and central sensitisation musculoskeletal LBP together.
MEthods And AnAlysIs
study design
This is a two-arm randomised, double-blind, placebo-con- trolled clinical trial. The study will be coordinated at the King Fahd Hospital of the University. All participants will be recruited from the hospital (patients referred to the depart- ment, additionally flyers will be distributed inviting people to participate). This study is funded through the Imam Abdulrahman Bin Faisal University (IAU; grant number 2017–308-CAMS). Ethical approval has been obtained from the institutional review board (IRB) of the IAU (IRB‐ 2017‐03–129). This study is prospectively registered with the Australian New Zealand Clinical Trials Registry (Registration Number ACTRN12618000921280). Table 1 shows Trial Registration Data Set. This trial protocol has been prepared according to the Standard Protocol Items: Recommendations for Interventional Trials checklist state- ment (see online supplementary appendix 1).49
sample size and power calculation
Sample size calculation was based on two sample t-tests. We used R function power.t.test via R V.3.4.1 (https:// cran.r-project.org). A total sample size of 200 (100 in each arm) will achieve 90% power to detect a mean difference of percentage reduction in NRS pain of 10% between the two treated arms at week 24. The mean percentage reduc- tion in NRS pain is assumed to be 15% in the control arm (patient treated with SHAM programme) and 25% in
Open access
patients who receive PLFMF therapy. A 0.2 SD is consid- ered along with a two-sided significance level (alpha) of 5% using a two-sample equal-variance t-test. The sample size allows for 15% of patients lost to follow-up at week 24. A 10% absolute reduction in NRS pain at week 24 will translate into an expected effect size of 0.5. This means the NRS score of the average person in the active PLFMF arm is 0.5 the SD above the average person who have had sham treatment, and hence exceed the scores of 69% of the control group.
The 38-item clinical criteria checklist developed by Smart et al11–13 will be used to classify patients into different phenotypes of musculoskeletal CLBP. This method of discriminative validity was established.11–13 All patients will be analysed collectively. Subgroup anal- ysis will be performed to assess the effect of PLFMF on subtypes of pain.
statistical analysis
All randomised patients will be analysed on the inten- tion-to-treat basis. Safety analyses will be performed for all patients who received at least one treatment session. Data will be coded and entered into SPSS (version 23; IBM Corp., USA) programme for analysis. Baseline char- acteristics will be presented by treatment group. Binary and categorical variables will be summarised by frequen- cies and percentages. Percentages will be calculated according to the number of patients for whom data are available. Where values are missing, the denominator, which will be less than the number of patients assigned to the treatment group, will be reported either in the body or a footnote of the summary table. Continuous variables will be summarised by mean and SD as well as by quar- tiles. Before summarising continuous outcomes, a test of normality will be performed. If the outcome is normally distributed, it will be summarised by mean (SD) in each arm and the difference between arms will be tested using t-test. However, if no evidence of normality, data will be summarised using the median (IQR). In such case, the Wilcoxon rank sum test will be used to test the difference between arms.
Treatment effect for the primary and continuous secondary outcomes will be assessed through analysis of covariance adjusted for the baseline measurement score. Overall treatment effect over time on all contin- uous outcomes, repeatedly collected over the course of the study, will be estimated using mixed linear models to take into account the correlation within each individual. The mixed linear model will include random intercept adjusted with the baseline score, time as categorical and the interaction between treatment and time. P values will not be adjusted for multiplicity. However, the outcomes are clearly categorised by degree of importance (primary, main secondary and other secondary) and a limited number of subgroup analyses are pre-specified.
Categorical binary efficacy measures will be primarily analysed using logistic regression. All tests will be two-sided with p values less than 0.05 will be considered significant.
Abdulla FA, et al. BMJ Open 2019;9:e024650. doi:10.1136/bmjopen-2018-024650
3
|
