Acute Non-specific Low Back Pain
Conditions
Keywords
Low back pain, Milgamma, NSAIDs
Brief summary
The purpose of this study is to assess the effectiveness and safety of add-on Milgamma®/ Milgamma® compositum step-therapy in patients with acute non-specific low back pain receiving modern NSAIDs in routine medical practice.
Detailed description
This is a multi-centre observational prospective study that was planned for assessment the effectiveness of neurotropic vitamins therapy with Milgamma®/ Milgamma® compositum in combination with modern NSAIDs (preferential/selective cyclooxygenase-2 (COX-2) inhibitors) in patients with acute non-specific back pain. Approximately 500 adult out-patients with acute non-specific low back pain who have been prescribed therapy consisting of (1) modern NSAIDs (preferential/selective COX-2 inhibitors) or (2) modern NSAIDs (preferential/selective COX-2 inhibitors) + Milgamma® / Milgamma® compositum will be enrolled in the study. Each patient will be observed over a period of approximately 94 days. 9 visits/phone contacts are planned to be conducted during this period. Information about patient's condition, pain intensity, pain flare-ups, satisfaction with the treatment, patient's disability, therapy used for acute back pain treatment, data on safety will be collected during these contacts. Pain intensity will be measured with Numeric Rating Scale (NRS), patients' disability will be evaluated with Roland Morris disability questionnaire, patients' satisfaction with the treatment will be assessed with 5-point verbal rating scale. Safety assessment will be based on frequency and severity of adverse drug reactions recorded during the study. Prior to the start of the study, neurologists (potential investigators) will be asked to fill out feasibility questionnaires to identify their individual routine practice regarding prescription or non-prescription of Milgamma® / Milgamma® compositum. Based on results of feasibility physicians will be divided to non-prescribers and prescribers of Milgamma® / Milgamma® compositum to the patients with acute non-specific low back pain. In each medical institution, such non-prescribers and prescribers will be proposed to participate in the study. Non-prescribers will be responsible for enrolling group (1) (NSAIDs alone), prescribers will be responsible for enrolling group (2) (NSAIDs + Milgamma® / Milgamma® compositum).
Interventions
DRUGExposure of interest (within routine clinical practice):Vitamin B complexes Milgamma® and Milgamma® compositum
Milgamma®: 2 mL injection solution containing thiamin hydrochloride 100 mg, pyridoxine hydrochloride 100 mg, cyanocobalamin 1 mg, lidocaine hydrochloride 20 mg. Milgamma® compositum: 1 tablet containing benfotiamine 100 mg, pyridoxine hydrochloride 100 mg.
Sponsors
Woerwag Pharma LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent including data protection declaration according to the local legislation. * Acute non-specific low back pain less than 21 days (= 3 weeks). * Low back pain treatment with (1) modern NSAIDs (preferential/selective COX-2 inhibitors) or (2) modern NSAIDs (preferential/selective COX-2 inhibitors) + Milgamma®/ Milgamma® compositum prescribed (but not started yet) in frames of routine medical practice. * Prescribed (but not started yet) step-therapy with Milgamma® to be followed by Milgamma® compositum in accordance with locally approved instruction for medical use (for the group planned to be treated with Milgamma®/ Milgamma® compositum step-therapy). * Pain intensity according to Numerical Rating Scale (NRS) ≥4 points ≤9 at the time of enrollment. * In case of presence of previous episodes of acute non-specific low back pain in medical history, the last one had resolved at least 30 days before the start of current episode.
Exclusion criteria
* History or presence of any disease that, in the opinion of the investigator, might confound the results of the study, poses an additional risk to the subject during participation in the study or can change pain perception (examples of such possible conditions: any malignancy, stomach ulcer, duodenal ulcer, chronic heart failure, bronchial asthma, psychiatry disorders, epilepsy, Parkinson Disease etc). * Spinal surgery/rehabilitation in the last 12 months. * Acute back pain that is attributable to any known or suspected specific identifiable cause (e.g. discogenic radiculopathy, spondylolisthesis, osteomalacia, inflammatory arthritis, metabolic, neurological diseases or tumor). * Severe scoliosis. * Use of NSAIDs or vitamins B within 2 months prior to enrollment into the study. * Necessity to use myorelaxants or antidepressants for treatment of acute non-specific low back pain. * Prior use of non-pharmacological treatment (physiotherapy, heat treatment (e.g. heat patch, hot water bottle) or topically applied medicinal products to the back area, procaine blocks) within the last 3 days before study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Pain Intensity After 10 Days of Treatment | Baseline; Visit 3 (10 days after the start of treatment) | Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Pain intensity was measured at baseline and at 10 days after the start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Pain Intensity Over Time | From Baseline to Visit 5 (38 days after the start of treatment) | Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Pain intensity was measured at baseline, at 5, 10, 24 and 38 days after the start of treatment. A mixed model repeated measures was used to analyze change from baseline in pain intensity over time from Baseline to Visit 5 (38 days after the start of treatment) in each group. The model included a random effect for subject and fixed effect terms for treatment, visit, treatment-by-visit interaction, baseline pain intensity. An unstructured covariance structure was used to model the within-subject errors. P-value was calculated for the difference between treatment groups. |
| Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Visit 2 (5 days after the start of treatment); Visit 3 (10 days after the start of treatment); Visit 4 (24 days after the start of treatment) and Visit 5 (38 days after the start of treatment) | Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Relief in pain intensity was defined as 100%\*(pain intensity at baseline - pain intensity at Visit 2, 3, 4 or 5)/ pain intensity at baseline. Percentage of patients showing at least 30% low back pain relief at Visit 2 (5 days after the start of treatment), at Visit 3 (10 days after the start of treatment), at Visit 4 (24 days after the start of treatment) and at Visit 5 (38 days after the start of treatment) were calculated separately. |
| Change in Pain-related Disability After 10 Days of Treatment | Baseline; Visit 3 (10 days after the start of treatment) | Patients' disability was assessed using Roland Morris disability questionnaire (RMDQ). RMDQ is a 24-item self-administered disability measure in which greater level of pain-related disability is reflected by higher score. The RMDQ score ranges from 0 to 24 with a lower score indicating better function. |
| Percentage of Patients With at Least One Pain Flare-up During the Study | From Visit 5 (38 days after the start of treatment) to Visit 9 (End of Study Visit, 94 days after the start of treatment) | Episode of pain flare-up was defined as presence of at least 1 day with low back pain following a period without pain lasting at least 4 weeks. Therefore pain flare-ups were registered no earlier than 4 weeks after the start of treatment, i.e. starting from Visit 5 (38 days after the start of treatment). The occurrence of pain flare-up was determined by the investigator. |
| Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | From Visit 5 (38 days after the start of treatment) to Visit 9 (End of Study Visit, 94 days after the start of treatment) | Episode of pain flare-up was defined as presence of at least 1 day with low back pain following a period without pain lasting at least 4 weeks. Therefore pain flare-ups were registered no earlier than 4 weeks after the start of treatment, i.e. starting from Visit 5 (38 days after the start of treatment). The occurrence of pain flare-up was determined by the investigator. Percentages of patients with at least one pain flare-up resulting in consultancy with physician or professional management, resulting in disruption of daily activity, and resulting in NSAIDs intake were analyzed separately. |
| Number of Treatment Days With NSAIDs | From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit | Number of treatment days with NSAIDs was calculated using the data collected on the NSAIDs intake during the study irrespective of the specific drug used. Duration of each intake period was determined as Stop date - Start date +1 and, finally, all individual duration values were summed up. In case medication intake was ongoing at the End of Study Visit, stop date was imputed by the date of study completion. |
| Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Baseline; Visit 2 (5 days after the start of treatment), Visit 4 (24 days after the start of treatment); Visit 5 (38 days after the start of treatment) | Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Pain intensity was measured at baseline, at 5, 24 and 38 days after the start of treatment.Changes of pain intensity from baseline to Day 5, from baseline to Day 24 and from baseline to Day 38 after the start of treatment were calculated separately. |
| Prescribed and Actual Number of Treatment Days With Milgamma® Compositum | From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit | Prescribed number of treatment days with Milgamma® compositum intake was reported at Baseline visit. Actual number of treatment days was calculated by summing up all the individual periods of treatment with Milgamma® compositum (in days) reported starting from Visit 2. If the treatment was interrupted, the days patient did not receive Milgamma® compositum were not contribute to the total number of treatment days with Milgamma® compositum intake. |
| Patient Satisfaction With Treatment | Visit 2 (5 days after the start of treatment); Visit 3 (10 days after the start of treatment); Visit 5 (38 days after the start of treatment) and Visit 9 (94 days after the start of treatment) | Patient satisfaction with treatment was evaluated using a 5-point verbal rating scale (1= very dissatisfied, 2= dissatisfied, 3= neutral, 4= satisfied, 5= very satisfied) after 5, 10, 38 days and 3 months (94 days) since the start of treatment. |
| Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment | From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit | Percentage of patients prematurely discontinued prescribed treatment with Milgamma®/ Milgamma® compositum was evaluated by reasons for discontinuation. |
| Reasons for Early Discontinuation of Study Participation | From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit | Percentage of patient prematurely discontinued study participation by the following reasons: patient lost to follow-up, patient withdrew consent, administrative reasons, pain resolution, adverse event, death, other reason. |
| Frequency and Severity of Adverse Drug Reactions (ADRs) | From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit | As this was a non-interventional study in which NSAIDs and Milgamma® / Milgamma® compositum were administered and managed within routine medical care, safety assessment was based on frequency and severity of Adverse Drug Reactions (ADRs) recorded during the study. ADR was defined as an adverse event (AE) suspected to be causally related to the medicinal product (Milgamma®, Milgamma® compositum or NSAID). The severity grade (mild, moderate or severe) of ADR was determined based on the investigator's judgement. Adverse events not related to the medicinal product were not monitored in this observational study. |
| Prescribed and Actual Number of Milgamma® Injections | From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit | Prescribed number of Milgamma® injections was reported at Baseline visit. Actual number of injections was calculated by counting the number of injections administered and reported starting from Visit 2. If the treatment was interrupted, the days patient did not receive Milgamma® injections were not contribute to the total number of injections. |
Countries
Russia
Participant flow
Recruitment details
A total of 500 patients with acute non-specific low back pain were enrolled in the study at 56 clinical sites.
Participants by arm
| Arm | Count |
|---|---|
| NSAIDs Group Patients with acute non-specific low back pain prescribed with modern NSAIDs (preferential/selective COX-2 inhibitors) | 244 |
| NSAIDs+Milgamma+Milgamma Compositum Group Patients with acute non-specific low back pain prescribed with modern NSAIDs (preferential/selective COX-2 inhibitors) + Milgamma® / Milgamma® compositum Milgamma®: 2 mL injection solution containing thiamin hydrochloride 100 mg, pyridoxine hydrochloride 100 mg, cyanocobalamin 1 mg, lidocaine hydrochloride 20 mg.
Milgamma® compositum: 1 tablet containing benfotiamine 100 mg, pyridoxine hydrochloride 100 mg. | 250 |
| Total | 494 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other (long business trip) | 0 | 1 |
| Overall Study | Pain resolution | 0 | 4 |
| Overall Study | Screen failure | 6 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | NSAIDs Group | NSAIDs+Milgamma+Milgamma Compositum Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 244 Participants | 250 Participants | 494 Participants |
| Age, Continuous | 39.6 years STANDARD_DEVIATION 10.1 | 42.1 years STANDARD_DEVIATION 10.3 | 40.9 years STANDARD_DEVIATION 10.3 |
| Pain intensity and patients' disability at baseline Pain intensity at baseline | 6.6 units on a scale STANDARD_DEVIATION 1.2 | 6.7 units on a scale STANDARD_DEVIATION 1.1 | 6.6 units on a scale STANDARD_DEVIATION 1.2 |
| Pain intensity and patients' disability at baseline Patients' disability at baseline | 11.1 units on a scale STANDARD_DEVIATION 4.8 | 11.7 units on a scale STANDARD_DEVIATION 4.4 | 11.4 units on a scale STANDARD_DEVIATION 4.6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Russia | 244 participants | 250 participants | 494 participants |
| Sex: Female, Male Female | 143 Participants | 142 Participants | 285 Participants |
| Sex: Female, Male Male | 101 Participants | 108 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 244 | 0 / 250 |
| other Total, other adverse events | 1 / 244 | 5 / 250 |
| serious Total, serious adverse events | 0 / 244 | 0 / 250 |
Outcome results
Primary
Change of Pain Intensity After 10 Days of Treatment
Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Pain intensity was measured at baseline and at 10 days after the start of treatment.
Time frame: Baseline; Visit 3 (10 days after the start of treatment)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSAIDs Group | Change of Pain Intensity After 10 Days of Treatment | -5.1 units on a scale | Standard Deviation 1.8 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Change of Pain Intensity After 10 Days of Treatment | -4.0 units on a scale | Standard Deviation 1.7 |
Comparison: Since the superiority of one treatment over the other is investigated and taking into consideration that smaller negative values of the primary variable correspond to the greater reduction of pain, the statistical hypotheses are:~Null hypothesis (H0):~H0: μ2 - μ1 ≥ 0~Alternative hypothesis (HA):~HA: μ2 - μ1 \< 0, where μ1 и μ2 are the mean changes from baseline in pain intensity for (1) modern NSAIDs therapy and for (2) modern NSAIDs + Milgamma\\ Milgamma compositum therapy, correspondingly.p-value: <0.001ANCOVA
Secondary
Change in Pain-related Disability After 10 Days of Treatment
Patients' disability was assessed using Roland Morris disability questionnaire (RMDQ). RMDQ is a 24-item self-administered disability measure in which greater level of pain-related disability is reflected by higher score. The RMDQ score ranges from 0 to 24 with a lower score indicating better function.
Time frame: Baseline; Visit 3 (10 days after the start of treatment)
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSAIDs Group | Change in Pain-related Disability After 10 Days of Treatment | -8.4 units on a scale | Standard Deviation 4.6 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Change in Pain-related Disability After 10 Days of Treatment | -7.0 units on a scale | Standard Deviation 4 |
Comparison: Change from baseline in pain-related disability as measured by Roland Morris disability questionnaire at 10 days after the start of treatment was compared between groups using analysis of covariance (ANCOVA) model with treatment group as fixed factor and baseline value disability score as a covariate.p-value: <0.001ANCOVA
Secondary
Change of Pain Intensity After 5, 24 and 38 Days of Treatment
Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Pain intensity was measured at baseline, at 5, 24 and 38 days after the start of treatment.Changes of pain intensity from baseline to Day 5, from baseline to Day 24 and from baseline to Day 38 after the start of treatment were calculated separately.
Time frame: Baseline; Visit 2 (5 days after the start of treatment), Visit 4 (24 days after the start of treatment); Visit 5 (38 days after the start of treatment)
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NSAIDs Group | Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Change of pain intensity from baseline to Day 5 after the start of treatment | -3.1 units on a scale | Standard Deviation 1.5 |
| NSAIDs Group | Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Change of pain intensity from baseline to Day 24 after the start of treatment | -6.1 units on a scale | Standard Deviation 1.5 |
| NSAIDs Group | Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Change of pain intensity from baseline to Day 38 after the start of treatment | -6.3 units on a scale | Standard Deviation 1.4 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Change of pain intensity from baseline to Day 5 after the start of treatment | -2.4 units on a scale | Standard Deviation 1.3 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Change of pain intensity from baseline to Day 24 after the start of treatment | -5.3 units on a scale | Standard Deviation 1.8 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Change of Pain Intensity After 5, 24 and 38 Days of Treatment | Change of pain intensity from baseline to Day 38 after the start of treatment | -6.0 units on a scale | Standard Deviation 1.7 |
Comparison: Changes from baseline in pain intensity measured on 0-10 points NRS scale at 5, 24 and 38 days after were compared between groups using ANCOVA models similar to those used for the analysis of the primary variable.p-value: <0.001ANCOVA
Secondary
Change of Pain Intensity Over Time
Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Pain intensity was measured at baseline, at 5, 10, 24 and 38 days after the start of treatment. A mixed model repeated measures was used to analyze change from baseline in pain intensity over time from Baseline to Visit 5 (38 days after the start of treatment) in each group. The model included a random effect for subject and fixed effect terms for treatment, visit, treatment-by-visit interaction, baseline pain intensity. An unstructured covariance structure was used to model the within-subject errors. P-value was calculated for the difference between treatment groups.
Time frame: From Baseline to Visit 5 (38 days after the start of treatment)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| NSAIDs Group | Change of Pain Intensity Over Time | -5.1 units on a scale |
| NSAIDs+Milgamma+Milgamma Compositum Group | Change of Pain Intensity Over Time | -4.4 units on a scale |
p-value: <0.001ANCOVA
Secondary
Frequency and Severity of Adverse Drug Reactions (ADRs)
As this was a non-interventional study in which NSAIDs and Milgamma® / Milgamma® compositum were administered and managed within routine medical care, safety assessment was based on frequency and severity of Adverse Drug Reactions (ADRs) recorded during the study. ADR was defined as an adverse event (AE) suspected to be causally related to the medicinal product (Milgamma®, Milgamma® compositum or NSAID). The severity grade (mild, moderate or severe) of ADR was determined based on the investigator's judgement. Adverse events not related to the medicinal product were not monitored in this observational study.
Time frame: From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit
Population: Safety population was defined as all patients who signed informed consent for entry into the study and started the study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSAIDs Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had mild ADRs | 1 Participants |
| NSAIDs Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had moderate ADRs | 0 Participants |
| NSAIDs Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had severe ADRs | 0 Participants |
| NSAIDs Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had not any ADRs | 243 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had not any ADRs | 245 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had mild ADRs | 5 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had severe ADRs | 0 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Frequency and Severity of Adverse Drug Reactions (ADRs) | Patients who had moderate ADRs | 0 Participants |
Secondary
Number of Treatment Days With NSAIDs
Number of treatment days with NSAIDs was calculated using the data collected on the NSAIDs intake during the study irrespective of the specific drug used. Duration of each intake period was determined as Stop date - Start date +1 and, finally, all individual duration values were summed up. In case medication intake was ongoing at the End of Study Visit, stop date was imputed by the date of study completion.
Time frame: From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSAIDs Group | Number of Treatment Days With NSAIDs | 9.6 Days of treatment | Standard Deviation 4.4 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Number of Treatment Days With NSAIDs | 10.6 Days of treatment | Standard Deviation 8.9 |
Comparison: NSAIDs intake during the study was analyzed. In order to calculate the total number of treatment days with NSAIDs, first, intersecting or adjacent records were collapsed, irrespective of the specific drug used; the duration of each of the resulting intake periods was determined as (End date - Start date + 1) and, finally, all individual duration values were summed up. In case medication intake was ongoing at the end of study, end date was imputed by the date of study completion.p-value: 0.986Wilcoxon (Mann-Whitney)
Secondary
Patient Satisfaction With Treatment
Patient satisfaction with treatment was evaluated using a 5-point verbal rating scale (1= very dissatisfied, 2= dissatisfied, 3= neutral, 4= satisfied, 5= very satisfied) after 5, 10, 38 days and 3 months (94 days) since the start of treatment.
Time frame: Visit 2 (5 days after the start of treatment); Visit 3 (10 days after the start of treatment); Visit 5 (38 days after the start of treatment) and Visit 9 (94 days after the start of treatment)
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NSAIDs Group | Patient Satisfaction With Treatment | Visit 3 (10 days after the start of treatment) | 4.2 units on a scale | Standard Deviation 0.8 |
| NSAIDs Group | Patient Satisfaction With Treatment | Visit 2 (5 days after the start of treatment) | 3.8 units on a scale | Standard Deviation 0.8 |
| NSAIDs Group | Patient Satisfaction With Treatment | Visit 5 (38 days after the start of treatment) | 4.5 units on a scale | Standard Deviation 0.7 |
| NSAIDs Group | Patient Satisfaction With Treatment | Visit 9 (94 days after the start of treatment) | 4.6 units on a scale | Standard Deviation 0.6 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Patient Satisfaction With Treatment | Visit 9 (94 days after the start of treatment) | 4.7 units on a scale | Standard Deviation 0.5 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Patient Satisfaction With Treatment | Visit 5 (38 days after the start of treatment) | 4.5 units on a scale | Standard Deviation 0.6 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Patient Satisfaction With Treatment | Visit 2 (5 days after the start of treatment) | 3.8 units on a scale | Standard Deviation 0.6 |
| NSAIDs+Milgamma+Milgamma Compositum Group | Patient Satisfaction With Treatment | Visit 3 (10 days after the start of treatment) | 4.1 units on a scale | Standard Deviation 0.7 |
Comparison: Comparison of patient satisfaction with treatment between treatment groups after 5 days since the start of study treatment.p-value: 0.921Wilcoxon (Mann-Whitney)
Comparison: Comparison of patient satisfaction with treatment between treatment groups after 10 days since the start of study treatmentp-value: 0.051Wilcoxon (Mann-Whitney)
Comparison: Comparison of patient satisfaction with treatment between treatment groups after 38 days since the start of study treatmentp-value: 0.651Wilcoxon (Mann-Whitney)
Comparison: Comparison of patient satisfaction with treatment between treatment groups after 3 months since the start of study treatmentp-value: 0.106Wilcoxon (Mann-Whitney)
Secondary
Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment
Percentage of patients prematurely discontinued prescribed treatment with Milgamma®/ Milgamma® compositum was evaluated by reasons for discontinuation.
Time frame: From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit
Population: Safety population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSAIDs Group | Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment | Completed prescribed step-therapy | 226 Participants |
| NSAIDs Group | Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment | Prematurely discontinued due to adverse event | 2 Participants |
| NSAIDs Group | Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment | Prematurely discontinued due to pain resolution | 19 Participants |
| NSAIDs Group | Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment | Prematurely discontinued due to patient's decision | 2 Participants |
| NSAIDs Group | Percentage of Patients Prematurely Discontinued Milgamma®/ Milgamma® Compositum Treatment | Prematurely discontinued due to other reason | 1 Participants |
Secondary
Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment.
Pain intensity was measured using 0-10 point Numeric Rating Scale (NRS). NRS is 11-step scale for assessment of pain intensity at the moment of patient's examination ranging from 0 (no pain) to 10 (worst pain imaginable). Relief in pain intensity was defined as 100%\*(pain intensity at baseline - pain intensity at Visit 2, 3, 4 or 5)/ pain intensity at baseline. Percentage of patients showing at least 30% low back pain relief at Visit 2 (5 days after the start of treatment), at Visit 3 (10 days after the start of treatment), at Visit 4 (24 days after the start of treatment) and at Visit 5 (38 days after the start of treatment) were calculated separately.
Time frame: Visit 2 (5 days after the start of treatment); Visit 3 (10 days after the start of treatment); Visit 4 (24 days after the start of treatment) and Visit 5 (38 days after the start of treatment)
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSAIDs Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 5 after the start of treatment | 194 Participants |
| NSAIDs Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 10 after the start of treatment | 235 Participants |
| NSAIDs Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 24 after the start of treatment | 241 Participants |
| NSAIDs Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 38 after the start of treatment | 244 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 38 after the start of treatment | 241 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 5 after the start of treatment | 140 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 24 after the start of treatment | 240 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With 30% Low Back Pain Relief After 5, 10, 24 and 38 Days of Treatment. | Number and percentage of patients with 30% pain relief at Day 10 after the start of treatment | 214 Participants |
Comparison: For Visit 2 (5 days after the start of treatment) relief in pain intensity was defined as 100%\*(pain intensity at baseline - pain intensity at Visit 2)/ pain intensity at baseline. The denominator for the proportion of patients was the number of patients with available pain intensity measurements after imputation using Last observation carried forward (LOCF) method.p-value: <0.001Regression, Logistic
Comparison: For Visit 3 (10 days after the start of treatment) relief in pain intensity was defined as 100%\*(pain intensity at baseline - pain intensity at Visit 3)/ pain intensity at baseline. The denominator for the proportion of patients was the number of patients with available pain intensity measurements after imputation using Last observation carried forward (LOCF) method.p-value: <0.001Regression, Logistic
Comparison: For Visit 4 (24 days after the start of treatment) relief in pain intensity was defined as 100%\*(pain intensity at baseline - pain intensity at Visit 4)/ pain intensity at baseline. The denominator for the proportion of patients was the number of patients with available pain intensity measurements after imputation using Last observation carried forward (LOCF) method.p-value: 0.061Regression, Logistic
Secondary
Percentage of Patients With at Least One Pain Flare-up During the Study
Episode of pain flare-up was defined as presence of at least 1 day with low back pain following a period without pain lasting at least 4 weeks. Therefore pain flare-ups were registered no earlier than 4 weeks after the start of treatment, i.e. starting from Visit 5 (38 days after the start of treatment). The occurrence of pain flare-up was determined by the investigator.
Time frame: From Visit 5 (38 days after the start of treatment) to Visit 9 (End of Study Visit, 94 days after the start of treatment)
Population: Full Analysis Set (FAS). Denominator of proportion was the number of FAS patients who had at least one pain-free period during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NSAIDs Group | Percentage of Patients With at Least One Pain Flare-up During the Study | 35 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With at Least One Pain Flare-up During the Study | 10 Participants |
Comparison: Episode of pain flare-up was defined as presence of at least 1 day with pain following a period without pain lasting at least 4 weeks . The denominator for the proportion was the number of FAS patients who had at least one pain-free period with approximately 4 weeks duration registered during the study.p-value: <0.001Fisher Exact
Secondary
Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake
Episode of pain flare-up was defined as presence of at least 1 day with low back pain following a period without pain lasting at least 4 weeks. Therefore pain flare-ups were registered no earlier than 4 weeks after the start of treatment, i.e. starting from Visit 5 (38 days after the start of treatment). The occurrence of pain flare-up was determined by the investigator. Percentages of patients with at least one pain flare-up resulting in consultancy with physician or professional management, resulting in disruption of daily activity, and resulting in NSAIDs intake were analyzed separately.
Time frame: From Visit 5 (38 days after the start of treatment) to Visit 9 (End of Study Visit, 94 days after the start of treatment)
Population: Full Analysis Set (FAS). Denominator of proportion is the number of FAS patients who had at least one pain-free period and at least one pain flare-up episode during the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSAIDs Group | Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | Patients with at least one pain flare-up resulting in consultancy with physician | 4 Participants |
| NSAIDs Group | Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | Patients with at least one pain flare-up resulting in disruption of daily activity | 20 Participants |
| NSAIDs Group | Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | Patients with at least one pain flare-up resulting in NSAIDs intake | 19 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | Patients with at least one pain flare-up resulting in consultancy with physician | 4 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | Patients with at least one pain flare-up resulting in disruption of daily activity | 4 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Percentage of Patients With at Least One Pain Flare-up Resulting in Consultancy With Physician, Resulting in Disruption of Daily Activity, and Resulting in NSAIDs Intake | Patients with at least one pain flare-up resulting in NSAIDs intake | 8 Participants |
Comparison: Difference in proportion of patients with at least one pain flare-up resulting in consultancy with physician95% CI: [-3.6, 60.7]
Comparison: Difference in proportion of patients with at least one pain flare-up resulting in disruption of daily activity95% CI: [-51.6, 17.4]
Comparison: Difference in proportion of patients with at least one pain flare-up resulting in NSAIDs intake95% CI: [-4.1, 55.5]
Secondary
Prescribed and Actual Number of Milgamma® Injections
Prescribed number of Milgamma® injections was reported at Baseline visit. Actual number of injections was calculated by counting the number of injections administered and reported starting from Visit 2. If the treatment was interrupted, the days patient did not receive Milgamma® injections were not contribute to the total number of injections.
Time frame: From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NSAIDs Group | Prescribed and Actual Number of Milgamma® Injections | Prescribed exposure of Milgamma® injections | 9.3 number of injections | Standard Deviation 2.4 |
| NSAIDs Group | Prescribed and Actual Number of Milgamma® Injections | Actual exposure of Milgamma® injections | 9.3 number of injections | Standard Deviation 2.6 |
Secondary
Prescribed and Actual Number of Treatment Days With Milgamma® Compositum
Prescribed number of treatment days with Milgamma® compositum intake was reported at Baseline visit. Actual number of treatment days was calculated by summing up all the individual periods of treatment with Milgamma® compositum (in days) reported starting from Visit 2. If the treatment was interrupted, the days patient did not receive Milgamma® compositum were not contribute to the total number of treatment days with Milgamma® compositum intake.
Time frame: From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NSAIDs Group | Prescribed and Actual Number of Treatment Days With Milgamma® Compositum | Prescribed exposure of Milgamma® compositum | 30.1 Days of treatment | Standard Deviation 14.3 |
| NSAIDs Group | Prescribed and Actual Number of Treatment Days With Milgamma® Compositum | Actual exposure of Milgamma® compositum | 29.9 Days of treatment | Standard Deviation 13.2 |
Secondary
Reasons for Early Discontinuation of Study Participation
Percentage of patient prematurely discontinued study participation by the following reasons: patient lost to follow-up, patient withdrew consent, administrative reasons, pain resolution, adverse event, death, other reason.
Time frame: From Baseline to Visit 9 (End of Study Visit, 94 days after the start of treatment)/ Early Discontinuation Visit
Population: Safety population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to other reason | 0 Participants |
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients completed the study in accordance with the protocol | 244 Participants |
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients lost to follow-up | 0 Participants |
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients withdrew informed consent | 0 Participants |
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to administrative reasons | 0 Participants |
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to pain resolution | 0 Participants |
| NSAIDs Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to adverse event | 0 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to other reason | 1 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to administrative reasons | 0 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients completed the study in accordance with the protocol | 244 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to adverse event | 0 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients lost to follow-up | 0 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients discontinued study participation due to pain resolution | 4 Participants |
| NSAIDs+Milgamma+Milgamma Compositum Group | Reasons for Early Discontinuation of Study Participation | Patients withdrew informed consent | 1 Participants |