This was a double-blind, double-dummy, multicentric, parallel group, prospective, comparative, randomized study conducted at: J. J. Hospital, Mumbai; Indira Gandhi Government Medical College, Nagpur; Mahatma Gandhi Medical College and Hospital, Jaipur; and B. J. Medical College and Sassoon General Hospital, Pune. The study protocol was approved by the institutional review board at each centre, and all patients provided written informed consent prior to participation. The execution and monitoring of the study were conducted in accordance with the requirements of good clinical practice.
Subject selection criteria
Male and female patients in the age range of 18–70 years with localized, uncomplicated acute lumbosacral pain, associated with degenerative spinal disorders (confirmed radiologically), of recent onset [1–30 day(s)] and with pain intensity at rest of at least 6 on a 10-point visual analogue scale (VAS) were included in this study.
The following patients were excluded: those patients with suspicion of a serious underlying spinal condition such as sciatica and nonspecific back symptoms related to abdominal, pelvic or thoracic pathology; those with prior history of sensory and/or motor deficits in the lower extremities and lumbosacral facet syndrome; those with malignancy, osteoporosis or previous history of lumbar spine surgery; those with any possibly confounding severe pain relating to the back, fibromyalgia, symptomatic disc herniation, spondylolisthesis higher than grade 2, severe spinal stenosis, acute LBP due to prolapsed intervertebral disc (PID) and who had received aceclofenac or tizanidine therapy in the past 1 week before inclusion in the study. Patients with history of hypersensitivity to NSAIDS or tizanidine and those with prior history of asthma or hypersensitivity potentially requiring concomitant treatment, and had used steroids within 4 weeks of study entry, were excluded. Those patients requiring drugs that affect platelet functions and coagulation were excluded from the study. Patients with history of peptic ulcers, duodenal ulcers, gastrointestinal bleeding, or bleeding disorders were not recruited in this study. Patients with abnormal renal and liver function and with significant unstable medical disease were also excluded from the study. Pregnant and lactating women and females of childbearing potential, who did not use contraceptives, were not enrolled in this study. All patients underwent a detailed neurological examination involving the spine and lower extremities. Neurological examination was performed by the principal investigators at each centre who were blinded to the study medication.
Patients fulfilling the inclusion and exclusion criteria were randomized to a double-blind, double-dummy treatment for 7 days with aceclofenac (100 mg)–tizanidine (2 mg) fixed dose combination tablets b.i.d (with aceclofenac 100 mg placebo) or aceclofenac (100 mg) alone b.i.d (with aceclofenac 100 mg–tizanidine 2 mg fixed dose combination placebo).
The primary efficacy outcome measures included pain intensity on movement, at rest, at night and pain relief scores. The pain intensity was captured on a VAS ranging from “0 to 10” where a score of “0” represents “no pain” and “10” represents “worst” possible pain. Pain relief (relative to the amount of pain before enrolment) was assessed on a 5-point verbal rating scale with categories 1 = complete relief, 2 = good, 3 = moderate, 4 = slight, 5 = no relief. Pain intensity was measured on days 1 (baseline) 2, 3, 4, 5, 6 and 7. Pain relief was assessed on days 3 and 7.
The secondary efficacy outcome measures included functional impairment and global efficacy assessment. The functional impairment was assessed at all three visits (baseline, and days 3 and 7) using modified Schober’s test [16
] and lateral body-bending test [18
]. While performing the body-bending test, the patient was asked to stand with feet 15 cm apart. The position of the tips of the index finger was marked on the skin of both the thighs, and the patient was asked to bend maximally to the left and right side. The maximum reach of the index finger was marked on the skin of both the thighs. The distance between the upper and lower marks was measured on both the sides.
The patients’ and investigators’ overall assessment of study medication was recorded at the final visit using a 5-point verbal rating scale (0 = no change, 1 = poor, 2 = moderate, 3 = good, 4 = excellent).
Efficacy analyses were performed for the clinically evaluable patient population and safety analysis for all the randomized patients who received at least one dose of study medication. Patients from both the study groups were evaluated at baseline for homogeneity with respect to demographic and disease characteristics. The basic descriptive statistics were calculated.
The primary efficacy outcome measures were compared at baseline on days 3 and 7 using two sample t test. Test of proportions in contingency tables were made using χ2 test or, if the expected cell frequencies were small, it was compared by Fisher’s exact test. The statistical significance level was set at the level 0.05.
Patients who had received at least one dose of study medication were evaluated for safety assessment. Comparisons of the two groups with respect to changes in laboratory parameters were evaluated by t test or Mann–Whitney U test as appropriate. Statistical analysis was performed using statistical software MINITAB 14.