Trial reportClinical drug investigation2022
Efficacy and Safety of Tramadol Hydrochloride Twice-Daily Sustained-Release Bilayer Tablets with an Immediate-Release Component for Chronic Pain Associated with Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled, Treatment-Withdrawal Study.
Trial report in Clinical drug investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials.International journal of molecular sciences · 2023Pooled it
- Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023Trial
- Short- and Mid-Term Outcomes of Fixed-Dose Tramadol/Paracetamol in Early-Stage Symptomatic Knee Osteoarthritis: A Single-Center Retrospective Observational Extension Study.Life (Basel, Switzerland) · 2026Article
- Article
- Development, Physicochemical Characteristics and Pharmacokinetics of a New Sustained-Release Bilayer Tablet Formulation of Tramadol with an Immediate-Release Component for Twice-Daily Administration.European journal of drug metabolism and pharmacokinetics · 2024Article
- Balancing the evidence: An update on analgesic use in rheumatic and musculoskeletal diseases.Frontiers in drug safety and regulation · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesKnee osteoarthritis pain is a chronic form of pain for which conventional non-steroidal anti-inflammatory drugs may provide insufficient analgesia. Twice-daily tramadol hydrochloride (65% sustained-release/35% immediate-release) bilayer tablets are a novel formulation of tramadol developed for managing chronic pain. The objectives of this study were to examine the effectiveness and safety of this formulation in patients with chronic knee osteoarthritis pain.
methodsThis was a multicenter, randomized, placebo-controlled, double-blind, parallel-group, treatment-withdrawal study. Patients with a reduction in Numeric Rating Scale (NRS) for pain of ≥2 points during a 1-3-week, open-label, tramadol dose-escalation period (100-300 mg/day) were randomized to continue tramadol or switched to placebo for 4 weeks (double-blind period). Patients with inadequate efficacy (increase in NRS ≥2 points/patient request) were withdrawn. Outcomes included the time to inadequate analgesic efficacy from randomization (primary endpoint), the cumulative retention rate, and safety.
resultsOverall, 249 and 160 patients entered the dose-escalation and double-blind periods, respectively (tramadol 79; placebo 81). Kaplan-Meier analysis revealed superiority of tramadol (log-rank p = 0.042), and a hazard ratio of 0.50 (95% confidence interval [CI] 0.25-0.99). Documentation of an inadequate analgesic effect was less frequent in the tramadol group (15.4%, 95% CI 8.2-25.3% vs. 30.9%, 95% CI 21.1-42.1%). The cumulative retention rate was greater in the tramadol group (83.7% vs. 69.0%). Adverse events occurred in 80.6% (200/248) of patients in the open-label period, and in 38.5% (30/78) and 13.6% (11/81) of patients in the tramadol and placebo groups, respectively, in the double-blind period. Opioid-associated adverse events, such as nausea, vomiting, constipation, somnolence, and dizziness, were the most frequent events.
conclusionThis study demonstrated the analgesic efficacy and safety of sustained-release tramadol tablets with an immediate-release component for chronic knee osteoarthritis pain.
trial registrationJapicCTI-132103 (Japan Pharmaceutical Information Center; registration date February 25, 2015).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.