Efficacy and Safety of Etoricoxib/Cyanocobalamin Versus Etoricoxib for Acute Low Back Pain

Efficacy and Safety of the Fixed-Dose Combination of Etoricoxib/Cyanocobalamin Versus Etoricoxib in the Treatment of Patients with Acute Low Back Pain

Phase III longitudinal, multicenter, randomized, double-blind clinical trial. The aim of this study is to evaluate the efficacy and safety of the Fixed-Dose Combination of Etoricoxib/Cyanocobalamin Versus Etoricoxib in Patients With Acute Low Back Pain

Study Overview

• Status: Completed
• Conditions: Acute Low-back Pain
• Intervention / Treatment: Drug: Etoricoxib + Cyanocobalamin fixed dose; Drug: Etoricoxib fixed dose

Detailed Description

Researchers will compare the fixed-dose combination of Etoricoxib/Cyanocobalamin versus Etoricoxib in acute low back pain by comparing the proportion of patients that reported an improvement in pain during the 7 days of follow up. The adverse events related to the interventions will be registered during follow up.

Participants will:

• Be randomized into one of the 2 intervention groups (A or B)
• Visit the clinic in 3 occasions (day 0, day 3 of follow up and day 7 of follow up)
• In case needed the patient could take 50 mg of tramadol, as a rescue medication, previous authorization of de principal investigator

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 11000
    • Laboratorio Silanes, S.A. de C.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Agree to participate in the study and give written informed consent
• Patient with pain reported as moderate to severe intensity with ≥ 40 mm on the Visual Analog Scale (VAS).
• At least 4 points on the "Douleur Neuropathique-4 items" (DN-4) scale.
• Diagnosis of acute low back pain as a first-time episode or a previous episode 6 months before the enrollment day and lasting no more than 6 weeks.
• Women of childbearing potential under a medically acceptable method of contraception

Exclusion Criteria:

• Patients participating in another clinical trial involving an investigational treatment or participation in one within 4 weeks prior to study start
• Patients in whom the participation in the study may be influenced (employment relationship with the research site or sponsor, inmates, etc.)
• At medical discretion, a disease that affects prognosis and prevents outpatient management, for example, but not limited to: end-stage cancer, kidney, heart, respiratory or liver failure, mental illness or with scheduled surgical or hospital procedures
• History/presence of any disease or condition that, in the opinion of the Investigator, could pose a risk for the patient or confusing the efficacy and safety of the investigational product
• Patients in whom the study drug is contraindicated for medical reasons
• Patients with allergy or hypersensitivity to the active substance of the study drugs, related products or excipients (Etoricoxib of Cyanocobalamin)
• Pregnant women, women breastfeeding or planning a pregnancy during the conducting the study
• Significant history of gastrointestinal diseases (e.g., gastric ulcer, Crohn's disease, Ulcerative Colitis, etc.)
• Active opioid and/or NSAID treatment including COX-2 inhibitors, reported in the medical record within the last 72 hours of study entry.
• Patients with a history of congestive heart failure: NYHA II-IV.
• Concomitant use of strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, etc.).
• Patients with a history of alcohol or drug abuse in the last year
• Patients with a history of ischemic heart disease, peripheral artery disease, and/or cerebral vascular disease (including patients who have recently undergone coronary revascularization or angioplasty)
• Patients with a history of seizures, epileptic status and/or grand mal seizures
• History of chronic liver failure Child-Pugh A, B, and/or C
• History of acute renal failure (glomerular filtration rate <30 ml/min/1.72 m2)
• Patient with a history of chronic pain associated with fibromyalgia, Paget's disease or bone pain induced by metastatic cancer
• Low back pain due to a history of major trauma in the past 12 months (e.g., vertebral fracture, post-traumatic spondylolisthesis) or due to a visceral disorder (e.g., dysmenorrhea, history of endometriosis).
• Patients with symptoms suggestive of COVID-19 infection (fever, cough, dyspnea) and/or contact in the last 14 days with a suspected or positive patient for COVID-19

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etoricoxib+Cyanocobalamin; Administered orally, 1 tablet a day for 7 days.	Drug: Etoricoxib + Cyanocobalamin fixed dose; One tablet of 90 mg / 0.50 mg a day; Other Names: Etori + Cyano
Active Comparator: Etoricoxib; Administered orally, 1 pill a day for 7 days.	Drug: Etoricoxib fixed dose; One pill of 90 mg a day; Other Names: Etori

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events through the patient's diary record.	To describe the frequency, intensity and causality of the adverse events presented during the clinical trial by treatment group. The adverse events will be registered by the patient in the diary record. Each adverse event will be followed up at the discretion of the researcher.	7 dyas
Comparison of the proportion of patients reporting pain improvement (reduction in pain intensity with a VAS ≤20 mm) at 1, 3, 5, and 7 days of follow-up, according to their baseline measurement in each treatment group	The visual analog pain scale (VAS) is a straight line in which one end signifies absence of pain and the other means the worst pain imaginable. The researcher will apply the VAS scale to each patient at each visit to assess pain intensity. At the end of the clinical trial the change porcentage will be measured and compared between treatment groups. The patient will visit the clinic at days 0,3 and 7. The researcher will call the patient for follow up at days 1 and 5.	7 dyas

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analyze the average change in pain intensity according to VAS score at 1, 3, 5, and 7 days in each treatment group and in comparison with the baseline measurement.	The visual analog pain scale (VAS) is a straight line in which one end signifies absence of pain and the other means the worst pain imaginable. The researcher will apply the VAS scale to each patient at each visit to assess pain intensity. At the end of the clinical trial the change porcentage will be measured and compared between treatment groups. The patient will visit the clinic at days 0,3 and 7. The researcher will call the patient for follow up at days 1 and 5.	7 days
Analyze the percentage change in pain intensity based on VAS score at 1, 3, 5, and 7 days in each treatment group and in comparison with the baseline measurement.	% change= ((Final Measurement-Initial Measurement)/(Initial Measurement))*100	7 days
Comparison of the proportion of subjects with pain improvement (reduction in pain intensity) through VAS, ≥ 30% at 1, 3, 5, and 7 days in each treatment group and in comparison with the baseline measurement.	The visual analog pain scale (VAS) is a straight line in which one end signifies absence of pain and the other means the worst pain imaginable. The researcher will apply the VAS scale to each patient at each visit to assess pain intensity. The proportion of patiens with an improvement of pain >30% will be reported and compared between treatment groups at days 1,3,5 and 7.	7 days
Comparison of the proportion of subjects with pain improvement (reduction in pain intensity) through VAS, ≥ 50% at 1, 3, 5, and 7 days in each treatment group and in comparison with the baseline measurement.	The visual analog pain scale (VAS) is a straight line in which one end signifies absence of pain and the other means the worst pain imaginable. The researcher will apply the VAS scale to each patient at each visit to assess pain intensity. The proportion of patiens with an improvement of pain >30% will be reported and compared between treatment groups at days 1,3,5 and 7.	7 days
Assess and compare the degree of physical disability due to acute low back pain, measured through the Oswestry disability questionnaire at 1, 3, 5, and 7 days in each treatment group and in comparison with the baseline measurement.	The Oswestry questionnaire has been designed to give us information as to how the back pain has affected the ability to manage everyday life of patients, it classifies QOL as: no disability, mild disability, moderate disability, severe disability and completely disabled. The disability degree would be compared.	7 days
Assess and compare the degree of disability to perform daily activities due to low back pain, reported through Roland-Morris questionnaire at 1, 3, 5, and 7 days in each treatment group and in comparison with the baseline measurement.	The Roland-Morris questionnaire has been designed to assess the activities of daily living functional mobility pain. A maximum score of 24 indicates the greatest degree of disability from pain. The disability degree will be compared.	7 days
Assess changes in the score on the "Douleur Neuropathique-4 items" scale (DN-4) at days 3 and 7 in each treatment group and in comparison with the baseline measurement.	The DN4 is a clinician-administered, neuropathic pain diagnostic questionnaire, consisting of ten items grouped in four sections. The first seven items are related to the quality of pain (burning, painful cold, electric shocks) and its association to abnormal sensations (tingling, pins and needles, numbness, itching). The other three items are related to neurological examination in the painful area (touch hypoesthesia, pinprick hypoesthesia, tactile allodynia).	7 days
Report the number of patients who present therapeutic failure during the study among the treatment groups	Therapeutic failure will be defined by the principal researcher previous medical consult, the following criteria must be present: - When there is a decrease <10 mm or increase in VAS values compared to baseline and a ≥ 80% adherence to treatment	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To report the percentage of therapeutic adherence at day 7 of the intervention in each treatment group.	Therapeutic adherence will be defined by the principal researcher. Adherence to treatment will be defined as a consumption ≥ 80% of the doses that the patient should have ingested at the time of the corresponding evaluation.	7 days
Report the number of patients who require the use of rescue medication during the clinical trial in each treatment group	The rescue medication will be tramadol 50 mg: - The patient that considers the need for rescue medication must call the doctor, who will be in charge of applying the VAS scale by telephone. If the doctor considers it necessary, the taking of the rescue medication will be indicated.	7 days

Collaborators and Investigators

• Sponsor: Laboratorios Silanes S.A. de C.V.
• Investigators: Principal Investigator: Ricardo Choza-Romero, MD, Centro de Atención e Investigación Clínica S.C.; Principal Investigator: Adelfia Urenda-Quezada, MD, Servicios Avanzados de Investigación Medica Mediadvance S.C.; Principal Investigator: Isabel E Rucker Joerg, MD, Clinical Research Institute S.C.; Principal Investigator: Jesus H Mendoza-Ramírez, MD, Unidad Clínica de Bioequivalencia, S. de R.L. de C.V.

Publications and helpful links

General Publications

• Smeets R, Koke A, Lin CW, Ferreira M, Demoulin C. Measures of function in low back pain/disorders: Low Back Pain Rating Scale (LBPRS), Oswestry Disability Index (ODI), Progressive Isoinertial Lifting Evaluation (PILE), Quebec Back Pain Disability Scale (QBPDS), and Roland-Morris Disability Questionnaire (RDQ). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S158-73. doi: 10.1002/acr.20542. No abstract available.
• Mibielli MA, Geller M, Cohen JC, Goldberg SG, Cohen MT, Nunes CP, Oliveira LB, da Fonseca AS. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009 Nov;25(11):2589-99. doi: 10.3111/13696990903246911.
• Pallay RM, Seger W, Adler JL, Ettlinger RE, Quaidoo EA, Lipetz R, O'Brien K, Mucciola L, Skalky CS, Petruschke RA, Bohidar NR, Geba GP. Etoricoxib reduced pain and disability and improved quality of life in patients with chronic low back pain: a 3 month, randomized, controlled trial. Scand J Rheumatol. 2004;33(4):257-66. doi: 10.1080/03009740410005728.
• Bacchi S, Palumbo P, Sponta A, Coppolino MF. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Antiinflamm Antiallergy Agents Med Chem. 2012;11(1):52-64. doi: 10.2174/187152312803476255.
• Martina SD, Vesta KS, Ripley TL. Etoricoxib: a highly selective COX-2 inhibitor. Ann Pharmacother. 2005 May;39(5):854-62. doi: 10.1345/aph.1E543. Epub 2005 Apr 12.
• Takemoto JK, Reynolds JK, Remsberg CM, Vega-Villa KR, Davies NM. Clinical pharmacokinetic and pharmacodynamic profile of etoricoxib. Clin Pharmacokinet. 2008;47(11):703-20. doi: 10.2165/00003088-200847110-00002.
• Chiu CK, Low TH, Tey YS, Singh VA, Shong HK. The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial. Singapore Med J. 2011 Dec;52(12):868-73.
• Letizia Mauro G, Lauricella L, Vecchio M, Tomasello S, Scaturro D. Efficacy and tolerability of a fixed dose combination of cortex phospholipid liposomes and cyanocobalamin for intramuscular use in peripheral neuropathies. Minerva Med. 2019 Oct;110(5):455-463. doi: 10.23736/S0026-4806.19.06068-3.
• Zhang YF, Ning G. Mecobalamin. Expert Opin Investig Drugs. 2008 Jun;17(6):953-64. doi: 10.1517/13543784.17.6.953.
• Peracchi M, Bamonti Catena F, Pomati M, De Franceschi M, Scalabrino G. Human cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor. Eur J Haematol. 2001 Aug;67(2):123-7. doi: 10.1034/j.1600-0609.2001.t01-1-00507.x.
• Mauro GL, Martorana U, Cataldo P, Brancato G, Letizia G. Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study. Eur Rev Med Pharmacol Sci. 2000 May-Jun;4(3):53-8.
• Calderon-Ospina CA, Nava-Mesa MO, Arbelaez Ariza CE. Effect of Combined Diclofenac and B Vitamins (Thiamine, Pyridoxine, and Cyanocobalamin) for Low Back Pain Management: Systematic Review and Meta-analysis. Pain Med. 2020 Apr 1;21(4):766-781. doi: 10.1093/pm/pnz216.
• Antoniou K, Malamas M, Drosos AA. Clinical pharmacology of celecoxib, a COX-2 selective inhibitor. Expert Opin Pharmacother. 2007 Aug;8(11):1719-32. doi: 10.1517/14656566.8.11.1719.
• Shukla AK, Jhaj R, Misra S, Ahmed SN, Nanda M, Chaudhary D. Agreement between WHO-UMC causality scale and the Naranjo algorithm for causality assessment of adverse drug reactions. J Family Med Prim Care. 2021 Sep;10(9):3303-3308. doi: 10.4103/jfmpc.jfmpc_831_21. Epub 2021 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2024
• Primary Completion (Actual): October 4, 2024
• Study Completion (Actual): October 11, 2024

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Acute pain; Etoricoxib; Cyanocobalamin; Acute Low -back Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Micronutrients; Vitamin B Complex; Vitamins; Hematinics; Cyclooxygenase 2 Inhibitors; Etoricoxib; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: SIL-30952-III-23(1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No