Efficacy of Etoricoxib on Peripheral Hyperalgesia

Efficacy of Etoricoxib in Patients With Neuropathic Pain With and Without Peripheral Hyperalgesia - A Prove of Concept Trial

The purpose of the study is to determine the efficacy of etoricoxib on pain patients. The investigators assume that patients with neuropathic pain will have greater pain relief then patients on placebo.

Study Overview

• Status: Terminated
• Conditions: Radiculopathy; Postherpetic Neuralgia; Causalgia; Peripheral Nerve Injury; Polyneuropathy
• Intervention / Treatment: Drug: Etoricoxib; Drug: placebo

Detailed Description

Animal experiments analysing anti-hyperalgesic effects of Coxibs show inconsistent results due to different used dosages and varying different pain models. Theoretical the use of NSAIDs is rational, particularly of Coxibs as a part of the neuropathic pain management. But in the newest topical review, there is no valid information available about the effectiveness of these drugs in human neuropathic pain models or in patients with different underlying mechanism, e.g. with or without hyperalgesia.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44789
      • Bergmannsheil department of pain therapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 18 years with
• Persistent moderate or severe pain (> 4 on NRS (1..10)) at rest (average of three daily assessments using a diary for at least two days) .
• Neuropathic pain associated with a clinical and neurologically proven peripheral nerve injury, radiculopathy, postherpetic neuralgia or polyneuropathy or CRPS

• One of the two following QST phenotypes at the baseline assessment:

  • signs of peripheral hyperalgesia (that means, pathological decreased heat pain threshold and/or pathological decreased muscle pain threshold)
  • without signs of peripheral hyperalgesia (no pathological decreased heat - and/or muscle pain threshold)
• Patients of both gender
• Signed consent form
• Patients with the ability to understand and follow the instructions of the doctor

Exclusion Criteria:

• Excluded will be patients Parkinson's disease or a history of cerebral vascular insult or nerve injury.

Excluded will be also all patients with contradictions for the use of Etoricoxib:

• Hypersensitivity to the active substance or to any of the excipients.
• Active peptic ulceration or active gastrointestinal (GI) bleeding.
• Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetyl-salicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.
• Pregnancy and lactation
• Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).
• Estimated renal creatinine clearance <30 ml/min.
• Inflammatory bowel disease.
• Congestive heart failure (NYHA II-IV).
• Patients with hypertension whose blood pressure is persistently elevated above 140/90mmHg and has not been adequately controlled
• Established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.

• Intake of one of the following drugs (current or in the last 3 days)

  • selective-serotonin-reuptake-inhibitor
  • cetoconazole
  • rifampicin
  • phenytoin
  • carbamazepine
  • dexamethasone or other systemic corticoids
  • traditional nonsteroidal antiphlogistics
  • cyclooxygenase-inhibitors
  • immunosuppressives
  • TNF-α-inhibitors

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: etoricoxib, peripheral hyperalgesia; 14 patient with neuropathic pain and peripheral hyperalgesia get etoricoxib 90mg for 8 days	Drug: Etoricoxib; the patients get etoricoxib 90mg for 8 days. They get one pill with 90mg per day; Other Names: Arcoxia
Active Comparator: etoricoxib, no peripheral hyperalgesia; 14 patients with neuropathic pain without peripheral hyperalgesia get etoricoxib 90mg for 8 days	Drug: Etoricoxib; the patients get etoricoxib 90mg for 8 days. They get one pill with 90mg per day; Other Names: Arcoxia
Placebo Comparator: placebo, peripheral hyperalgesia; 14 patients with neuropathic pain with peripheral hyperalgesia get placebo for 8 days	Drug: placebo; patients get one pill of placebo (sugar-pill) per day for 8 days.
Placebo Comparator: placebo, no peripheral hyperalgesia; 14 patients with neuropathic pain without peripheral hyperalgesia get placebo for 8 days	Drug: placebo; patients get one pill of placebo (sugar-pill) per day for 8 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Superior improvement of peripheral hyperalgesia at day six after initiation of Cox-2-inhibiting-medication in comparison to placebo	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of the average on-going pain	reduction of the average on-going pain decrease of the neuropathic symptoms intensity (NPSI score) decrease of the patients global impression of change (PGIC) decrease of the frequency and cumulative 7 day dosage of rescue medication	12 month

Collaborators and Investigators

• Sponsor: Ruhr University of Bochum
• Investigators: Study Director: Christoph Maier, Dr.med, University hospital Bergmannsheil department of pain therapy

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 16, 2010
• First Submitted That Met QC Criteria: March 16, 2010
• First Posted (Estimate): March 17, 2010

Study Record Updates

• Last Update Posted (Estimate): August 24, 2012
• Last Update Submitted That Met QC Criteria: August 23, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: CRPS; Polyneuropathy; Causalgia; post herpetic neuralgia; Etoricoxib; peripheral nerve injury; radiculopathy; Morbus Sudeck; Nervenverletzung; postherpetische Neuralgie; COX-2-Inhibitor
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Autonomic Nervous System Diseases; Sensation Disorders; Somatosensory Disorders; Complex Regional Pain Syndromes; Neuralgia; Radiculopathy; Polyneuropathies; Hyperalgesia; Neuralgia, Postherpetic; Causalgia; Peripheral Nerve Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Etoricoxib
• Other Study ID Numbers: Etoricox09-10; 2009-015496-27 (EudraCT Number)