Evaluation of Tricortin 1000, Diclofenac Sodium, and Paracetamol in Chronic Low Back Pain: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-512292-12-00
- Protocol
- EQ06.17.01
- Sponsor
- Fidia Farmaceutici S.p.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to demonstrate the **superiority** of Tricortin 1000 over placebo in improving pain relief, measured as a change from baseline to 15 days, in patients with chronic low back pain (LBP) and acute exacerbation at study entry. This objective is clinically relevant as it aims to establish an effective treatment option for managing pain in patients suffering from chronic LBP, a condition that significantly impacts quality of life and functional ability.
Secondary objectives include:
- Comparing Tricortin 1000 and diclofenac sodium medicated plaster (Itami®) in terms of pain relief improvement from baseline to 15 days in patients with chronic LBP and acute exacerbation.
- Comparing Tricortin 1000 with placebo and diclofenac sodium medicated plaster in terms of functional disability improvement, clinical improvement, patient global assessment (PGA), clinical global impression (CGI), consumption of rescue medication, and patient safety, as changes from baseline to 15 days.
Participants
The clinical trial focuses on individuals diagnosed with **chronic low back pain** experiencing acute exacerbation. The study population includes both male and female participants aged between 40 and 70 years. Participants are required to have a **Body Mass Index (BMI)** of less than 30 kg/m² and must be able to maintain a diary throughout the study. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants were selected based on their ability to discontinue certain medications, such as analgesics, NSAIDs, opioids, and others that might interfere with study assessments, except for paracetamol. Additionally, participants must not have used Tricortin 1000 previously for low back pain or other conditions. The trial includes individuals who are able to read and understand the study material, comply with study requirements, and have provided informed consent. Both genders are included, and the study considers a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **double-dummy**, placebo- and active-controlled study to evaluate the effectiveness of Tricortin 1000 in patients with chronic low back pain. The primary objective is to demonstrate the superiority of Tricortin 1000 over placebo in improving pain relief from baseline to 15 days. The trial will involve multiple study visits, starting with an inclusion (screening) visit, followed by a baseline visit, and subsequent follow-up visits on Day 7 and Day 15. The end-of-study visit will coincide with the final follow-up on Day 15. The expected duration of participant involvement is approximately 15 days, with conditions for early termination including non-compliance with study requirements or adverse events that necessitate withdrawal.
Participants will be randomly assigned to receive either Tricortin 1000, a placebo, or an active comparator. The trial will assess primary and secondary endpoints, including the mean change in pain scores using the NRS-11 scale and improvements in low back pain-related disability measured by the Oswestry Low Back Pain Disability Index. Safety assessments will include physical examinations, vital signs, and monitoring of adverse events. The trial is estimated to conclude by December 31, 2025, with recruitment having started on March 25, 2019. Participants must meet specific inclusion criteria, such as a clinical diagnosis of chronic mechanical low back pain confirmed by imaging, and must not have used Tricortin 1000 previously for low back pain or other conditions. The study is conducted under strict ethical guidelines, ensuring informed consent and adherence to regulatory standards.
Treatment
The clinical trial involves the evaluation of several treatments, including the experimental medication **TRICORTIN 1000**, which is a solution for injection containing **cyanocobalamin** and **phospholipid from cerebral cortex**. This medication is administered via **intramuscular use**. The pharmaceutical form is a solution for injection, with a maximum daily dose of 2 ml and a total maximum dose of 30 ml over a treatment period of 15 days. The medication is of chemical origin and is not a paediatric formulation.
Another treatment used in the trial is **ITAMI 140 mg cerotto medicato**, a medicated plaster containing **diclofenac sodium**. This comparator treatment is applied topically, with a maximum daily dose of 280 mg and a total maximum dose of 4200 mg over a 15-day period. The product is also of chemical origin and is not intended for paediatric use.
The trial also includes **ACETAMOL adulti 500 mg compresse**, which is a tablet formulation containing **paracetamol**. This auxiliary treatment is administered orally, with a maximum daily dose of 2 g and a total maximum dose of 40 g over a 37-day period. Like the other treatments, it is of chemical origin and not designed for paediatric patients.
Two placebo treatments are utilized in the study: **Placebo 1 - injectable solution** and **Placebo 2 - plaster**. These placebos are used to maintain the double-blind nature of the trial. The placebo injectable solution is administered without a specified route, while the placebo plaster is applied topically. Both placebos are not paediatric formulations and do not contain active substances.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the mean change from baseline to Day 15 in the **NRS-11** (Numeric Rating Scale for pain). This primary endpoint will provide a quantitative measure of pain relief in patients with chronic low back pain. Secondary endpoints include the improvement in low back pain-related disability, which will be measured using the Oswestry Low Back Pain Disability Index (ODI), version 2.1a. This assessment will occur at the baseline visit and subsequently at Day 7 and Day 15. Additional clinical improvements will be evaluated through parameters such as Range of Motion testing, Joint reflex changes, Lasegue’s test, Femoral stretch test, Dandy’s sign, and Valleix’s points pressure, also assessed at baseline, Day 7, and Day 15.
Patient Global Assessment (PGA) and Clinical Global Impression (CGI) of the status of low back pain will be evaluated at the same time points. The requirement for daily rescue medication for pain relief will also be monitored. Safety assessments will include the evaluation of daily intramuscular Tricortin 1000 injections and twice-daily diclofenac sodium medicated plaster applications. These will be assessed through physical examinations, vital signs, and tracking the number of patient withdrawals and adverse events at each visit. The schedule for these assessments is designed to ensure comprehensive data collection and analysis, facilitating a robust evaluation of the treatment's efficacy and safety.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Clinical diagnosis of chronic 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).
- A moderate to severe acute exacerbation of chronic LBP at study entry, defined as a score ≥4 and ≤8 rated on the NRS-11
- Age greater than or equal to 40 and less than or equal to 70 years
- Patient able to maintain a Diary during the study
- Patient with a Body Mass Index (BMI) < 30 kg/m2
- 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 the exception of paracetamol, with no intent to resume during study
- Patients who did not receive antidepressant medications and/or benzodiazepines for at least 60 days
- 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
- Patient has undergone the informed consent process and has signed an approved consent form
- If female, patient must have a negative urine pregnancy test and use a highly effective form of contraception for a 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
- Patients who did not use Tricortin 1000 in the past to treat LBP or other pathological conditions
Exclusion Criteria
- Patients suffering of chronic non-specific LBP
- Participation in another research study
- History of epilepsy
- Patients who have an unstable psychiatric condition
- Unexplained serious thoracic pain
- Any recent trauma, which may raise the possibility of a fracture
- Fever and unexplained weight loss
- Bladder or bowel dysfunction
- Females who are pregnant or breast-feeding
- Patients who are not able to give informed consent
- Patients who cannot commit to the entire duration of the study
- Patients with back pain referred from a mechanical cause (except for mild, moderate degenerative process of disc and facet) non spinal source or back pain associated with another specific spinal cause
- Patients who have a primary bone disease, cancer, infection (except for osteoporosis patients without fracture history)
- Other conditions which may confound the interpretation of the study, such as rheumatoid arthritis, severe venous diseases, peripheral arterial diseases, transient ischemic attack, stroke, current symptoms of coronary artery disease
- History of narcotic abuse at any time in the past and/or drug or alcohol abuse in the past year
- Patients who have had a previous treatment with physical therapy for LBP in the last 4 weeks before the screening visit or are going through a course of physical therapy or chiropractic treatment at the time of planned enrolment
- History of carcinoma
- Progressive neurological deficit
- Disturbed gait, saddle anaesthesia
- Radicular syndromes of idiopatic, metabolic, toxic, infective, demyelinating or neoplastic aetiology
- Patients with spondylolisthesis, spondylolysis or ankylosing spondylitis
- Patients with scoliosis of 15° or more
- Patients with inflammatory arthritis or severe degenerative process of disc and facet
- Patients who have had prior spine surgery, including rhizotomy as like as, patients who are planning or have been advised to have spine surgery
- Patients with any concomitant chronic disease(s) or condition(s) that may predispose them to a high probability of interfering with the completion of the follow-up of the study such as peptic ulcer, liver disease, severe coronary disease, renal disease, cancer, pregnancy, alcoholism, mental state, or other clinically significant condition
- Patients with history of active or suspected oesophageal, gastric, pyloric channel, or duodenal ulceration or bleeding in the last 12 weeks before the screening visit
- Patients requiring chronic use of analgesia for pain
- Patients with known allergies or hypersensitivity or intolerance to Tricortin 1000, NSAIDs and/or paracetamol, and/or to active or inactive excipients of formulation
- Patients in treatment with neuroleptics (antipsychotics)
- Patients affected by diabetic neuropathy, multiple sclerosis or Amyotrophic Lateral Sclerosis
- Any contraindications to either prone distraction or side posture manipulation
- Any contraindications as reported in the Patient Information Leaflet of Tricortin 1000 or Diclofenac sodium medicated plaster
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 25 Mar 2019 | 300 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TRICORTIN 1000 “12 mg+1 mg/2 ml soluzione iniettabile per uso intramuscolare” | Test | SOLUZIONE INIETTABILE PER USO INTRAMUSCOLARE | INTRAMUSCULAR USE | 2 | 15 | PRD520280 |
ITAMI 140 mg cerotto medicato | Comparator | CEROTTO MEDICATO | TOPICAL USE | 280 | 15 | PRD3355726 |
Placebo 1 - injectable solution | Placebo | N/A | — | — | — | N/A |
Placebo 2 - plaster | Placebo | N/A | — | — | — | N/A |
ACETAMOL adulti 500 mg compresse | Other | COMPRESSE | ORAL USE | 2 | 37 | PRD373594 |