Modulation of the Surgical Inflammatory Response by Etoricoxib: Peripheral Versus Central
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- To test the hypothesis that orally administered etoricoxib (COX-2 inhibitor) modulates prostaglandin and cytokine synthesis in the central nervous system (CNS) and in the periphery in surgical patients.
研究概览
简要总结
The purpose of this study is to test the hypothesis that orally administered etoricoxib (COX-2) modulates prostaglandin and cytokine synthesis in the central nervous system (CNS) and in the periphery in surgical patients and thus reduces pain and suffering.
详细描述
This study will be a multiple centre, double-blind, placebo-controlled, randomized, parallel group study conducted in male and female adult patients undergoing elective primary single hip arthroplasty. In part 1 of the study 12 patients will be enrolled in the study and will be administrated 120 mg Etoricoxib or placebo orally on day one post surgery. The results from part 1 should help to adjust sampling time points (for blood, cerebrospinal fluid and hip drain fluid) if necessary. In part 2 of the study 40 patients will be enrolled and should receive 120 mg etoricoxib or placebo two hours before and 24 hours after surgery.
Primary end points will be the inflammatory mediators on peripheral and central levels. After surgical manipulation we expect increased mediators on both sides. It will be investigated if the medication could reduce the mediators compared to placebo and if the effect is related to pharmacokinetic parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject undergoing elective primary single hip arthroplasty
- •Subject diagnosed with Osteoarthritis / arthrosis
- •Subject has not taken non-steroidal anti-inflammatory drugs within 4 of their terminal half life times prior to enrollment
- •Subject capable of understanding and cooperating with the requirements of the study
排除标准
- •Patients with renal insufficiency (serum creatinine >1.5 mg/dl)
- •Recent major trauma or systemic infection (within 3 months)
- •Use of corticosteroid medication or chronic opioids (within 3 months)
- •Any other condition likely to affect prostaglandin and cytokine levels
- •Participation in another clinical study or receipt of an investigational drug within 30 days
- •Hypersensitivity to any component of the etoricoxib and/or placebo tablets
- •Uncontrolled hypertension defined as systolic blood pressure >140 mm Hg and diastolic pressure >90 mm Hg at rest after two repeated measurements
- •Congestive heart failure (NYHA II-IV)
- •Cerebrovascular disease
- •Established ischemic heart disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty)
- •Patients with any kind or severity of cirrhosis of the liver or cholestasis or elevated liver function enzymes (ALT or AST 3 fold) as a sign of clinical significant liver malfunction (corresponds to any Child-Pugh-Score ≥5)
- •Patients who have developed signs of asthma, acute rhinitis, nasal polyps, angioneurotic oedema or urticaria following the administration of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs)
- •Pregnancy and lactation
- •Patients with active peptic ulcerations or active gastro-intestinal (GI) bleeding
- •Inflammatory bowel disease
- •Recent history (within the last year) of alcohol or other substance abuse
- •An employee of the sponsor or study site
- •Any neurological syndrome or any other condition leading to contra-indication to spinal anesthesia
研究组 & 干预措施
A, 1
Study part 1 (n = 8)
干预措施: Etoricoxib 60 mg (Drug)
A, 2
Study part 1 (n = 4)
干预措施: Placebo for Etoricoxib 60 mg (Drug)
B, 1
Study part 2 (n = 20)
干预措施: Etoricoxib 60 mg (Drug)
B, 2
Study part 2 (n = 20)
干预措施: Placebo for Etoricoxib 60 mg (Drug)
结局指标
主要结局
To test the hypothesis that orally administered etoricoxib (COX-2 inhibitor) modulates prostaglandin and cytokine synthesis in the central nervous system (CNS) and in the periphery in surgical patients.
时间窗: within 24 hours post dosing (study part 1) and within 48 hour post dosing (study part 2)
次要结局
- To determine the CSF (cerebrospinal fluid), plasma and tissue pharmacokinetics of orally administered etoricoxib.(within 24 hours post dosing (study part 1) and within 48 hours post dosing (study part 2))
- To correlate the prostaglandin and cytokine response to clinical outcome parameters after hip arthroplasty.(within 4 days post dosing (study part 1 and 2))
- To assess the safety (via clinical laboratory tests and adverse events) of a single dose of 120 mg Etoricoxib for one day (Part1) or for two days (Part2) and placebo.(within 4 days post dosing (study part 1 and 2))