Milgamma® and Milgamma® Compositum Step-therapy in Patients With Acute Non-specific Low Back Pain Receiving Modern NSAID
- Conditions
- Acute Non-specific Low Back Pain
- Registration Number
- NCT03892707
- Lead Sponsor
- Woerwag Pharma LLC
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 500
- 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.
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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 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.
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.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.
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.
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.
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.
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.
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.
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.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.
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.
Trial Locations
- Locations (21)
LLC "Center for Medical Prevention and Rehabilitation treatment "Kamkor"
🇷🇺Ekaterinburg, Russian Federation
LLC "Research Medical Complex "Vashe Zdorovie"
🇷🇺Kazan, Russian Federation
Regional State Budgetary Institution of Health "Regional Clinical Hospital № 1" named after Prof. S.I. Sergeev
🇷🇺Khabarovsk, Russian Federation
State Healthcare Institution "Republican Clinical Neurological Center"
🇷🇺Kazan, Russian Federation
Federal State Healthcare Institution "Russian Scientific Center of Surgery named after academician B.V. Petrovsky"
🇷🇺Moscow, Russian Federation
LLC "Medicina"
🇷🇺Moscow, Russian Federation
Non-state Healthcare Institution "Central Clinical Hospital No. 2 named after N.A. Semashko of the JSC Russian Railways
🇷🇺Moscow, Russian Federation
LLC "Clinical Diagnostic Center Avitsena"
🇷🇺Naberezhnye Chelny, Russian Federation
LLC "Licon Plus"
🇷🇺Naberezhnye Chelny, Russian Federation
LLC "Medis"
🇷🇺Nizhny Novgorod, Russian Federation
JSC "MEdical Center Avitsenna", group of companies "Mother and Child"
🇷🇺Novosibirsk, Russian Federation
LLC "Multidisciplinary center of modern medicine "Euromed"
🇷🇺Omsk, Russian Federation
LLC "MRI-Expert Novosibirsk"
🇷🇺Novosibirsk, Russian Federation
Federal State Healthcare Institution St. Petersburg Clinical Hospital of the Russian Academy of Sciences
🇷🇺Saint Petersburg, Russian Federation
Out-patient clinic of SUE St. Petersburg Metropoliten
🇷🇺Saint Petersburg, Russian Federation
LLC "MD Project 2010"
🇷🇺Ufa, Russian Federation
LLC "National Medical Holding Medstandart"
🇷🇺Ufa, Russian Federation
Volgograd State Medical University
🇷🇺Volgograd, Russian Federation
LLC "Center of Evidence-Based Medicine"
🇷🇺Yaroslavl, Russian Federation
State Healthcare Institution of Yaroslavl Region "Clinical Hospital №8"
🇷🇺Yaroslavl, Russian Federation
LLC Medical Center "Nebolit"
🇷🇺Mytishchi, Moscow Region, Russian Federation