Low Back Pain, Mechanical
Conditions
Keywords
Chronic, Degenerative process of disc and facet
Brief summary
PAES, double blind, double dummy, multicenter, randomized, controlled clinical study to demonstrate superiority of Tricortin 1000 over placebo in improvement in pain relief as change from baseline to 15 days in patients with chronic low back pain (LBP).
Detailed description
This is a PAES, double blind, double dummy, multicenter, randomized, controlled clinical study, which will consist of a Screening phase (Visit 1) of up to 14 days and a Follow-up phase of up to 15 days. A total of 300 patients of either sex, aged between 40 and 70 years with diagnosis of chronic mechanical (mild, moderate degenerative process of disc and facet) LBP for at least 3 months but no more than 6 months will be randomized. Two stratification groups will be distinguished: the first group will be comprised of patients with chronic mechanical LBP due to mild, moderate degenerative process of disc and facet from 40 to \<55 years, the second group will be comprised of patients with chronic mechanical LBP due to mild-moderate degenerative process of disc and facet ≥55 to 70 years. All patients will be required to have diagnosis of chronic LBP with clinically and imaging confirmation of mechanical (mild, moderate degenerative process of disc and facet). Baseline assessments include: pain assessment and functional disability, clinical parameters, patient global assessment (PGA), clinical global impression (CGI) and consumption of rescue medication. Eligible patients will then be randomly assigned to one of the following three treatment arms: 1. Tricortin 1000 by intramuscular route (Arm A) 2. Diclofenac sodium medicated plaster by topical application (Arm B) 3. Placebo (Arm C) In arm A and B, Tricortin 1000 and Diclofenac sodium medicated plaster will be administered together with the alternate placebo, while patients in the placebo arm (Arm C) will be treated with both intramuscular and locally applied placebo. Patients will be in the study for approximately 30 days of trial duration with a treatment period of 15 days.
Interventions
DRUGTricortin 1000
Tricortin 1000 \[2 mL ampoules containing 12 mg of phospholipids and 1 mg of Vitamin B12 (Cyanocobalamin)\] will be administered intramuscular on the gluteus, once daily (24 hours apart), for 15 days starting from the evening of Day 0 (visit 2) plus Diclofenac sodium medicated plaster placebo will be applied twice daily (12 hours apart) for 15 days starting from the evening of Day 0 (visit 2), i.e. 30 applications.
DRUGItami
Diclofenac sodium 140 mg medicated plaster (Itami®) will be applied twice daily (12 hours apart) for 15 days starting from the evening of Day 0 (visit 2), i.e. 30 applications plus Tricortin 1000 placebo (2 mL ampoules) will be administered intramuscular on the gluteus, once daily (24 hours apart), for 15 days starting from the evening of Day 0 (visit 2).
DRUGPlacebo
Tricortin 1000 placebo (2 mL ampoules) will be administered intramuscular on the gluteus, once daily (24 hours apart), for 15 days starting from the evening of Day 0 (visit 2) plus Diclofenac sodium medicated plaster placebo will be applied twice daily (12 hours apart) for 15 days starting from the evening of Day 0 (visit 2), i.e. 30 applications.
Sponsors
Fidia Farmaceutici s.p.a.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind, double dummy
Intervention model description
PAES, double blind, double dummy, multicenter, randomized, controlled clinical study
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of mechanical (mild, moderate degenerative process of disc and facet) chronic LBP, for at least 3 months but no more than 6 months, confirmed (thanks to instrumental analysis obtained within 9 months before the Screening visit) by CT or MRI. In case a MRI/CT performed in the previous 9 months is not available, the diagnosis should be confirmed by means of a MRI performed between Screening visit (Visit 1) and Baseline visit (Visit 2) 2. A moderate to severe acute exacerbation of Chronic LBP at study entry, defined as a score ≥4 and ≤8 rated on the NRS-11 3. Age greater than or equal to 40 and less than or equal to 70 years 4. Patient able to maintain a Diary during the study 5. Patient with a Body Mass Index (BMI) \< 30 kg/m2 6. Discontinuation of any analgesic/NSAID therapy, opioids, corticosteroids, skeletal muscle relaxants and any other medication or non-pharmacological therapy (if it would interfere with the study assessments), with no intent to resume during study 7. Patients who did not receive antidepressant medications and/or benzodiazepines for at least 60 days 8. Patient able to read and understand the language and content of the study material, understand the requirements for follow-up visits, is willing to provide information at the scheduled evaluations and is willing and able to comply with the study requirements 9. Patient has undergone the informed consent process and has signed an approved consent form 10. If female, patient must have a negative urine pregnancy test and use a highly effective form of contraception for at least one month prior to screening and throughout the study; or females must be surgically sterile, or postmenopausal as documented in medical history for at least one year. Highly effective birth control methods include: combined hormonal contraception (containing estrogen and progestogen) associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence\* 11. Patients who did not use Tricortin 1000 in the past to treat LBP or other pathological conditions. * Note: According to 4.1 paragraph Birth control methods which may be considered as highly effective of the CTFG/Recommendations related to contraception and pregnancy testing in clinical trials Baseline Inclusion Criteria: 1. In aptients for which a MRI/CT performed in the previous 9 months is not available, the diagnosis of chronic LBP should be confirmed by means of a MRI performed between screening visit (Visit 1) and baseline (Visit 2) 2. LBP with score ≥ 5 and ≤ 8 in the NRS-11 (off medication except for paracetamol, study rescue medication) 3. Patient has discontinued use of all analgesic/NSAIDs, opioids, corticosteroids, skeletal muscle relaxants, and any other medication or non-pharmacological therapy (if it would interfere with the study assessments) at V1 (except for patients that will perform the MRI between Screening and Baseline visit) and agree not to resume them during study (except for paracetamol, study rescue medication). These medication must be discontinued for at least 14 days before the Baseline visit (Visit 2/ Day 0), i.e. can be taken for maximum 7 days during the 14-21 days of Screening phase, in case that the screening phase is prolonged up to 21 days in patients that will perform the MRI between screening and baseline visit. 4. Patient has complied with the requirements for rescue medication (no more than 4 tablets - 2 grams - of paracetamol per day up to 4 days per week) and no paracetamol intake in the 24 hours before baseline visit 5. Patient continues to meet all Screening inclusion/
Exclusion criteria
at the Baseline visit, with the exception of screening inclusion criterion 2 which is replaced by baseline inclusion criterion 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to 15 days in patients with chronic low back pain (LBP) and acute exacerbation at study entry using Numerical Rating Scale for pain | Day 15 | The primary efficacy endpoint will be the change from baseline to Day 15 in NRS-11 score.(0-10 points Numerical Rating Scale for pain, where score 0 corresponds to no pain and score 10 corresponds to unimaginable pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional disability improvement as change from baseline to 15 days through the Oswestry Low Back Pain Disability Index (ODI), version 2.1a | Day 0, Day 7 and Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster (Itami®) in functional disability improvement. LBP related disability improvement will be measured through the Oswestry Low Back Pain Disability Index (ODI), version 2.1a, at baseline visit and then in the following visits: V3-Day 7 and V4-Day 15. |
| Clinical improvement as change from baseline to 15 days | Day 0, Day7 and Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster (Itami®) in clinical improvement as change from baseline to 15 days. Clinical improvement will be evaluated at baseline visit and then at V3-Day 7 and V4-Day 15 through the following parameters: Range of Motion testing, Joint reflex changes (ROT), Lasegue's test (passive straight leg raise), Femoral stretch test (Wasserman test), Dandy's sign, Valleix's points pressure. |
| Patient global assessment PGA as change from baseline to 15 days. PGA:single-item measure:Considering all the ways that your LBP affect you,select one response for how you are doing at the moment:0=very well;1=well;2=fair;3=poor;4=very poor | Day 0, Day7 and Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster (Itami®) in patient global assessment (PGA) as change from baseline to 15 days. PGA will be evaluated at baseline visit and then in the following visits: V3-Day 7 and V4-Day 15 |
| ClinicalGlobalImpression as change from baseline to15days.CGI:7point scale clinician-rated(severity of illness)from1(normal)to7(severely ill).CGI score from1(very much improved)to7(very much worse).Treatment response consider efficacy and AEs | Day 0, Day7 and Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster (Itami®) in clinical global impression CGI as change from baseline to 15 days. CGI will be evaluated at baseline visit and then in the following visits: V3-Day 7 and V4-Day 15 |
| Improvement in pain relief as change from baseline to 15 days in patients with chronic LBP and acute exacerbation at study entry, using Numerical Rating Scale for pain | Day 15 | To compare Tricortin 1000 and diclofenac sodium medicated plaster (Itami®) in improvement in pain relief as change from baseline to 15 days in patients with LBP. (0-10 points Numerical Rating Scale for pain, where score 0 corresponds to no pain and score 10 corresponds to unimaginable pain) |
| Safety as change from baseline to 15 days evaluated by physical examination (body areas:Head;Ears;Eyes;Nose;Mouth;Skin;Heart;Lung;Lymph nodes;Genitourinary;Gastrointestinal;Skeletal;Neurological systems;Other, specify) | From Day -14 to Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster in patient safety as change from baseline to 15 days. |
| Safety as change from baseline to 15 days evaluated by vital signs (systolic blood pressure, diastolic blood pressure, heart rate) | From Day -14 to Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster in patient safety as change from baseline to 15 days. |
| Safety as change from baseline to 15 days evaluated by tracking the number of patient withdrawals and their adverse events | From Day -14 to Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster in patient safety as change from baseline to 15 days. |
| Consumption of rescue medication as change from baseline to 15 days using a patient diary (maximum 4 tablets for 4 days/week) | From Day -14 to Day 15 | To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster (Itami®) in consumption of rescue medication as change from baseline to 15 days. Daily rescue medication required for pain relief up to V4-Day 15 using a patient diary |
Countries
Italy
Contacts
Primary ContactFlavia Baruzzi
Backup ContactEmanuela Terragni
Outcome results
None listed