Procedures-evaluations
muscle spasm, LBP, Pain, pain
ADVERSE EVENTS
Pre-intervention evaluation included patient self-reported pain intensity assessment at rest using the VAS score (scoring range 0–100 mm), with higher scores indicating greater pain (“0 = No pain”; “100 = Worst imaginable pain”) and investigator evaluation of the muscle spasm using the finger-to-floor distance test. VAS scores were assigned individually by each patient. Other baseline procedures included the collection of patient sociodemographic and medical history data.The patients were then randomized 1:1 using permuted block randomization (FORTRAN90 IMSL) per site to receive a single deep intragluteal injection into the upper outer quadrant of either the test treatment (FDC diclofenac-thiocolchicoside) or the marketed solution containing 75 mg/3 ml of diclofenac (reference treatment, Voltaren®/Novartis). The assignment of treatment to patients according to the randomization scheme was operated centrally by the CRO that performed clinical monitoring. A separate randomization scheme was adopted for each site (i.e. randomization stratified by site). The randomization was performed using permuted blocks, i.e. random sequences of treatment allocations that contain the two treatments (A = investigational medicinal product or B = comparator) in a 1:1 ratio. Within a block, the sequence of treatment allocations was chosen at random from all possible permutations. The treatment allocation procedure consisted of preparing lists of permuted blocks for each center and reading off the next treatment allocation (Α-Test or Β-reference) from that list. Patients were allocated to treatments according to the screening number in ascending order. The personnel that made all contacts with patients and performed all clinical trial-related examinations was blinded to the block length with no access to the randomization scheme. The randomization scheme per site is included in the Then, pain intensity assessment using VAS by the patient and muscle spasm assessment by the investigator were performed at Intermediate (1 h post-injection) and Test of Cure visit (3 h post-injection). The investigators who administered the treatment also performed the clinical assessments. The efficacy assessments that were performed in this clinical trial were those which are traditionally used in patients with LBP. Safety parameters were evaluated at the End of Study Visit (24 h post-injection).The primary endpoint was the mean change in VAS from baseline to 3 h in subjects treated with the test treatment as compared to subjects treated with the reference treatment. However, in the analysis, the change from 3 h to baseline was used. Secondary outcome measures included the 1) mean change from baseline in the VAS score at 1 h post-administration, 2) the percentage of patients demonstrating > 30% reduction in pain intensity (as assessed via VAS score) at 1 and 3 h post-administration compared to baseline, 3) muscle spasm improvement assessed via the mean change of finger-to-floor distance from baseline at 1 and 3 h post-administration, and 4) the percentage of patients experiencing adverse events and withdrawn from the trial for safety reasons related to treatment. For the purpose of this manuscript, muscle spasm assessments (endpoint 3) are synoptically referred to, in order to minimize the potential introduction of bias from the effect of the test treatment (due to the presence of the muscle relaxant thiocolchicoside) versus the reference treatment.Based on literature review, an expert panel and a workshop during the “VIII International Forum on Primary Care Research on Low Back Pain” (Amsterdam, June 2006), for a range of commonly used back pain outcome measures, including VAS scale 0–100, a 30% improvement from baseline has been proposed as a useful threshold for identifying clinically meaningful improvement [