Clinical trial NCT06863636: Efficacy and Safety of Celecoxib/Acetaminophen Versus Celecoxib for Diagnosed Osteoarthritis in Acute Exacerbation
Official title: Efficacy and Safety Study of the Fixed-dose Combination of Celecoxib/Acetaminophen Compared to Celecoxib for the Treatment of Pain in Patients Diagnosed With Osteoarthritis in Acute Exacerbation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Joint Pain
Knee Osteoarthritis
Hip Osteoarthritis
Keywords: Joint pain
Knee Osteoarthritis
Hip Osteoarthritis
Acute pain
Lead sponsor: Laboratorios Silanes S.A. de C.V.
Sponsor class: INDUSTRY
First posted: 2025-03-07
Enrollment: 231
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, longitudinal, multicenter, randomized, double-blind clinical trial designed to evaluate the efficacy and safety of a fixed-dose combination of celecoxib and acetaminophen compared to celecoxib monotherapy for the treatment of pain associated with acute exacerbations of osteoarthritis.

Detailed description: Researchers will evaluate the efficacy and safety of a fixed-dose combination of celecoxib and acetaminophen compared to celecoxib monotherapy for the treatment of pain in patients with osteoarthritis experiencing an acute exacerbation over a 6-week follow-up period. Adverse events related to the study interventions will be recorded throughout the follow-up phase.

Participants will:

Be randomized into one of three intervention groups (A, B, or C).

Attend five scheduled clinic visits (Day 0, and Weeks 1, 2, 4, and 6 of follow-up).

Be permitted to take 500 mg of naproxen as rescue medication, if needed, with prior authorization from the principal investigator.

Eligibility criteria: Inclusion Criteria:

* Voluntarily agrees to participate in the study and provides written informed consent.
* Prior diagnosis of knee or hip osteoarthritis based on clinical criteria (according to the American College of Rheumatology (ACR) criteria described in Annex 5).
* Pain in the affected joint with exacerbation lasting no more than 3 weeks.
* Patient reports moderate to severe pain intensity (VAS ≥ 40 mm).
* For women of childbearing potential (a woman is considered fertile after menarche and until postmenopause unless permanently sterile), they must agree to use at least ONE of the following contraceptive methods during the study:

Barrier methods: diaphragm, cervical cap, male condom, female condom, spermicide foam, sponge, or film.

Hormonal methods: combined oral contraceptives, injectable contraceptives, subdermal implant, contraceptive patch.

Intrauterine device (IUD): copper or silver IUD, Levonorgestrel intrauterine system (IUS), and/or combinations of the above as deemed acceptable by the physician.

Women are considered not of childbearing potential if they meet at least ONE of the following criteria:

Postmenopausal. Premenopausal woman with at least ONE of the following: hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.

Male subjects must agree to use a male condom as a contraceptive method during the study.

* At the discretion of the Principal Investigator (PI) or treating physician, the subject has an indication for treatment with the investigational product and may derive clinical benefit from it.

Exclusion Criteria:

* Intolerance or allergy to the investigational product or any of its components (as reported in the medical history and patient interview).
* Participation in another clinical study involving an investigational treatment or participation in one within the last two weeks prior to the study start.
* Potential study bias due to employment or relationship with the research center, sponsor, or being part of a vulnerable population.
* Medical conditions affecting prognosis that prevent outpatient management, to be evaluated by the Principal Investigator for subject inclusion relevance.
* History of advanced, severe, progressive, or unstable disease of any kind that may interfere with efficacy and safety assessments or pose a special risk to the patient.
* Medical contraindication to the investigational product.
* History of allergic reaction to NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), Acetaminophen, or known hypersensitivity to any formulation components.
* Significant gastrointestinal disorders, such as gastric ulcers, Crohn's disease, ulcerative colitis, or gastrointestinal bleeding.
* Prior opioid treatment within the last five days, as reported in the medical history.
* History of treatment failure with COX-2 selective inhibitors, as documented in the medical history.
* History of chronic somatic pain unrelated to knee or hip osteoarthritis (e.g., fibromyalgia, metastatic disease, or Paget's disease).
* History of alcohol or drug abuse within the past year.
* Current treatment with NSAIDs, including COX-2 inhibitors, within the last 72 hours before signing informed consent (except for aspirin used for cardioprotective purposes).
* History of arthroscopy, viscosupplementation, or intra-articular steroid use in the last three months.
* Previous surgery on the affected joint within the last six months.
* Major trauma in the affected joint within the last three weeks.
* History of chronic liver failure (Child-Pugh A, B, or C).
* History of acute or severe renal failure (glomerular filtration rate \<30 ml/min/1.73 m²), as reported in the medical history.
* Significant coagulation disorders (e.g., Von Willebrand disease, hemophilia, vitamin K deficiency) or current use of anticoagulants.

Oncologic patients (except basal cell carcinoma) or those with severe illnesses that, according to the investigator, have a poor prognosis or a life expectancy of less than one year, including severe mental illness.

* Patients with symptoms suggestive of active COVID-19 infection (e.g., fever, cough, dyspnea) and/or contact within the last 14 days with a suspected or confirmed COVID-19 patient.
* Positive pregnancy test, pregnant women, those currently breastfeeding, or those planning pregnancy during the study period.

Primary outcomes:
measure: Comparison of the proportion of patients in each treatment group who, based on the baseline assessment, achieved a response according to the OMERACT-OARSI criteria at Weeks 1, 2, 4, and 6 of follow-up.
timeFrame: 6 weeks
measure: Number of participants Number of participants reporting treatment-related adverse events, as recorded in the patient diary.treatment-related adverse events through the patient's diary record.
timeFrame: 6 weeks
Secondary outcomes:
measure: To analyze the mean change in pain scores, as measured by the WOMAC questionnaire, at Weeks 1, 2, 4, and 6 compared to baseline, by treatment group.
timeFrame: 6 weeks
measure: To analyze the mean change in pain intensity, as measured by the Visual Analog Scale (VAS), at Weeks 1, 2, 4, and 6 compared to baseline, stratified by treatment group.
timeFrame: 6 weeks
measure: Comparison of the proportion of subjects in each treatment group who achieve a reduction of ≥30% in pain intensity, as measured by the Visual Analog Scale (VAS), at Weeks 1, 2, 4, and 6 compared to baseline.
timeFrame: 6 weeks
measure: To analyze the difference in SF-36 quality of life questionnaire scores at six weeks after the initiation of the intervention, compared to baseline, by treatment group.
timeFrame: 6 weeks
Other outcomes:
measure: To report the treatment adherence rate, expressed as a percentage, for each intervention group.
timeFrame: 6 weeks
measure: To describe the proportion of subjects experiencing therapeutic failure during the study, stratified by treatment group.
timeFrame: 6 weeks
measure: To report the proportion of patients requiring dose escalation during the follow-up period, stratified by treatment group.
timeFrame: 6 weeks
Locations:
city: Mexico City
country: Mexico
facility: Laboratorio Silanes, S.A. de C.V.
Study officials:
affiliation: Clinical Research Institute S.C.
name: Isabel E Rucker-Joerg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unidad de Medicina Especializada SMA
name: Ivonne A Torres-Quiroz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Servicios Avanzados de Investigación Médica Mediadvance, S.C.
name: Adelfia Urenda-Quezada, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Consultorio Médico "Dr. Rodrigo Suárez Otero"
name: Martha V Chavira-Flores, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IMACEN S.A. de C.V.
name: Rodrigo Suarez-Otero, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ebrahimzadeh MH, Makhmalbaf H, Birjandinejad A, Keshtan FG, Hoseini HA, Mazloumi SM. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in Persian Speaking Patients with Knee Osteoarthritis. Arch Bone Jt Surg. 2014 Mar;2(1):57-62. Epub 2014 Mar 15.
citation: Puljak L, Marin A, Vrdoljak D, Markotic F, Utrobicic A, Tugwell P. Celecoxib for osteoarthritis. Cochrane Database Syst Rev. 2017 May 22;5(5):CD009865. doi: 10.1002/14651858.CD009865.pub2.
citation: Krieckaert CL, van Tubergen A, Gehin JE, Hernandez-Breijo B, Le Meledo G, Balsa A, Bohm P, Cucnik S, Elkayam O, Goll GL, Hooijberg F, Jani M, Kiely PD, McCarthy N, Mulleman D, Navarro-Compan V, Payne K, Perry ME, Plasencia-Rodriguez C, Stones SR, Syversen SW, de Vries A, Ward KM, Wolbink G, Isaacs JD. EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2023 Jan;82(1):65-73. doi: 10.1136/annrheumdis-2022-222155. Epub 2022 May 12.
citation: Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.
citation: Busse JW, Bartlett SJ, Dougados M, Johnston BC, Guyatt GH, Kirwan JR, Kwoh K, Maxwell LJ, Moore A, Singh JA, Stevens R, Strand V, Suarez-Almazor ME, Tugwell P, Wells GA. Optimal Strategies for Reporting Pain in Clinical Trials and Systematic Reviews: Recommendations from an OMERACT 12 Workshop. J Rheumatol. 2015 Oct;42(10):1962-1970. doi: 10.3899/jrheum.141440. Epub 2015 May 15.
citation: Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, Callahan L, Copenhaver C, Dodge C, Felson D, Gellar K, Harvey WF, Hawker G, Herzig E, Kwoh CK, Nelson AE, Samuels J, Scanzello C, White D, Wise B, Altman RD, DiRenzo D, Fontanarosa J, Giradi G, Ishimori M, Misra D, Shah AA, Shmagel AK, Thoma LM, Turgunbaev M, Turner AS, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020 Feb;72(2):220-233. doi: 10.1002/art.41142. Epub 2020 Jan 6.