Efficacy and Safety of Pregabalin/Tramadol Combination Versus Pregabalin in Acute Pain of Neuropathic Origin

Study Overview
=================
Brief Summary
-----------------
Phase IIIb confirmatory study of efficacy and safety, longitudinal, multicenter, randomized, double-blind study of the combination Pregabalin/Tramadol versus Pregabalin in the management of acute pain of neuropathic origin.

Detailed Description
-----------------
Study to evaluate the efficacy and safety of the fixed-dose combination of Pregabalin/Tramadol versus Pregabalin in the management of acute pain of neuropathic origin. Patients who meet the inclusion criteria of the protocol and start treatment with the combination Pregabalin / Tramadol (75 mg / 50 mg) or Pregabalin 75 mg will be included. To evaluate the proportion of subjects who reported a success rate in the reduction of pain by 50%, the percentage of change in the pain intensity reported through the Visual Analog Pain Scale (VAS) will be calculated. This percentage will be categorized and the proportion of patients per treatment group will quantify. Changes in pain intensity during the intervention will be evaluated with the fixed-dose combination of Pregabalin/Tramadol (75 mg / 50 mg) or Pregabalin 75 mg, comparing the average difference in pain reported through VAS at days 1, 3, 5, 7, 10, 13 and 15 with respect to their baseline measurement. The mean change in reported neuropathic pain intensity across the DN4 questionnaire will also be evaluated, comparing its measurement on day 3, 10 and 15 with respect to the baseline, in each treatment group. At visit 1 (day 3) the need for dose escalation will be evaluated (Pregabalin/Tramadol (150 mg / 50 mg) or pregabalin (150 mg)) in both treatment groups, continuing with its follow-up in the evaluation of the intensity of pain reported by EVA and DN4. The proportion of subjects who started on the dose of Pregabalin / Tramadol (75 mg / 50 mg) or Pregabalin 75 mg, those that required adjustment of dose to treatment (Pregabalin / Tramadol (150 mg / 50 mg) or Pregabalin (75 mg)), as well as the proportion of patients who suspended the treatment. The percentage of adherence to the intervention by treatment group will be reported. The proportion of adverse events presented during the conduct of the study will be evaluated, regardless of the dose administered, to all the subjects who have received at least one dose of the investigational drug Which will be reported be reported through frequencies and percentages and classified according to frequency, gravity, severity (intensity) and the causality of the clinical manifestation.

Official Title
-----------------
Confirmatory Study of Efficacy and Safety of the Pregabalin/Tramadol Combination Versus Pregabalin in the Management of Acute Pain of Neuropathic Origin.

Conditions
-----------------
Neuropathic Pain

Intervention / Treatment
-----------------
* Drug: Pregabalin 75mg/ Tramadol 50 mg
* Drug: Pregabalin 75mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any gender. That the subject agrees to participate in the study and give its informed consent in writing. Age >18 years and ≤65 years of age at the start of the study. Neuropathic Pain Questionnaire (DN4) ≥ 4. Patients with proven tolerability (absence of moderate-serious adverse events) to pregabalin, defined by consumption of pregabalin 50 mg/day for 3 days. Women of childbearing age who have an acceptable method of contraception (eg barrier, oral hormonal, injectable, subdermal). Exclusion Criteria: Contraindication and known hypersensitivity to the use of pregabalin and/or tramadol. The patient is participating in another clinical study involving an investigational treatment or participated in any in the previous 4 weeks. In the medical opinion, a disease that affects the prognosis and prevents outpatient management, for example, but not limited or restricted to: terminal cancer, heart failure, obstruction gastrointestinal including paralytic ileus, suspected surgical abdomen, respiratory failure with scheduled surgical or hospital procedures. Positive pregnancy test, women who are pregnant, nursing or planning a pregnancy during the conduct of the study. Patients with a diagnosis of respiratory diseases: status asthmaticus, asthma, chronic obstructive pulmonary disease (COPD), cor pulmonale, acute respiratory depression, hypercapnia. Patients who are receiving monoamine oxidase inhibitors (MAOIs) or who have received within the last 2 weeks. Patients with a history of seizure disorders, epileptic status, and grand mal seizures. Patients with a history of severe depression of the central nervous system due to consumption of opiates. History of acute intoxications with hypnotics, opioid analgesics and psychotropics. History of alcohol or drug abuse (including opiates) in the last year according to DSM-V. Patients with a history of severe head trauma and/or brain edema. History/presence of any disease or condition which, in the opinion of the Investigator, could pose a risk to the patient or confound the efficacy and safety results of the study. Patients with symptoms suggestive of active COVID-19 infection (i.e., fever, cough, dyspnea) and/or contact in the last 14 days with a suspected or positive patient for COVID-19. Patients whose participation in the study may be influenced (employment relationship with the center investigator or sponsor, inmates, etc.).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Pregabalin/Tramadol<br>Fixed dose combination tablet of 75 mg Pregabalin and 50 mg of Tramadol, orally, every 12 hours. | Drug: Pregabalin 75mg/ Tramadol 50 mg<br>* Pharmaceutical Form: Tablet Dosage: 75 mg / 50 mg Administration way: oral<br>* Other names: LOBUXAL;|
| Active Comparator: Group B: Pregabalin<br>Monotherapy with 75 mg of Pregabalin, orally, every 12 hours. | Drug: Pregabalin 75mg<br>* Pharmaceutical Form: Capsule Dosage: 75 mg Administration way: oral<br>* Other names: Pregabalin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a success rate of >50% in pain reduction | Evaluate the proportion of subjects who reported a success rate of >50% in pain reduction at completion of the intervention, measure by the VAS (Visual Analog Scale) per treatment group. In a straight 10 centimeter line in which one end means no pain and the other end means the worst pain imaginable, the participants mark the amount of pain feeling at that moment. | 15 days | 
| Mean change in pain intensity by VAS (Visual Analog Scale) | Evaluate the mean change in pain intensity reported on days 1, 3, 5, 7, 10, 13, and 15 with respect to its baseline measurement, reported through the VAS (Visual Analog Scale) per treatment group. In a straight 10 centimeter line in which one end means no pain and the other end means the worst pain imaginable, the participants mark the amount of pain feeling at that moment. | Baseline,1,3,5,7,10, 13 and 15 days | 
| Mean change in pain intensity by DN4 questionnaire | Evaluate the mean change in pain intensity reported on days 3, 10 and 15 with respect to its baseline measurement according to the DN4 Questionnaire by treatment group. | Baseline, 3, 10 and 15 days | 
| Proportion of subjects requiring dose escalation | Evaluate the proportion of subjects who required dose escalation (from Pregabalin/Tramadol 75mg/50 to 150 mg/ 50 mg or Pregabalin 75mg to 150 mg, as appropriate) during the intervention, by treatment group. | Day 3 | 
| Frequency of adverse events | Compare the frequency of adverse events presented during the study between the treatment groups. | 15 days | 
| Intensity of adverse events. | Compare the intensity of adverse events presented by treatment group. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence percentage | Report the percentage of adherence to the intervention by treatment group, using the count of tablets returned to the research site | 15 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute pain, Neuropathic, Pregabalin, Tramadol