Prospective Randomized Multicentric Trial on Anti-TNFα Treatment and Infection Risk in the Perioperative Period During Elective Foot and Ankle Surgery in Patients With Rheumatoid Arthritis.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 660
- 试验地点
- 1
- 主要终点
- Surgical site infection
研究概览
简要总结
Rheumatoid arthritis (RA) is a frequent inflammatory arthritis that can lead to severe joint deformity and often requires orthopaedic surgical interventions. Anti-Tumor Necrosis Factor α (anti-TNFα) are biological disease-modifying antirheumatic drugs (DMARDs) increasingly used in the treatment of rheumatoid arthritis. An increased risk of opportunistic infection was demonstrated in patients treated with those drugs. This observation led many national committees to recommend anti-TNFα suspension in the perioperative period to avoid a raise in the postoperative infection risk in those patients. This approach is not supported by the data available in the current literature and it exposes patients to an increased risk of inflammatory flare ups of their disease during and after anti-TNFα suspension, which can compromise their postoperative rehabilitation and their quality of life.
The objective of this prospective randomized multicentric trial is to determine the effect of anti-TNFα suspension in the perioperative period on the postoperative infection risk. Overall, 660 rheumatoid arthritis patients requiring an elective foot or ankle surgery will be randomized into two groups. In the first group, anti-TNFα will be stopped 3 half-lives before the surgery while they will be continued in the second group. The postoperative infection rate will be compared between the two groups. Postoperative complication rates, flares and revision surgeries as well as the functional improvement will be compared.
The study hypothesis is that there is no significant difference in the risk of postoperative infection between the two groups.
Results from this study will help determine the optimal way to use anti-TNFα in the perioperative period and will therefore improve the quality of life of rheumatoid arthritis patients.
详细描述
A. STUDY DESIGN This is a prospective randomized multicentric trial. Patients will be randomized into two groups. Patients in Group A will continue their anti-TNF treatment during the whole perioperative period. Anti-TNFα medication will be suspended prior to the surgery in patients randomized in Group B. This design will allow us to minimize the important selection bias that was affecting the observational studies previously conducted on this topic. Due to safety concerns, patients and evaluators will not be blinded to the treatment.
B. RESEARCH LOCATION Considering the important number of patients required, we plan on conducting a multicentric study. This will allow us to recruit enough patients in a reasonable time frame to ensure sufficient power to our results. The main center where the data will be gathered is the CHU de Québec. Other centers in Canada will be invited to participate in the study for a maximum of 10 centers.
C. INTERVENTION Medication Patients randomized to Group A will continue their anti-TNFα treatment unaltered during the whole perioperative period. Surgery will be performed without consideration in regards to the timing of the treatment. The time elapsed between the last anti-TNFα administration and the surgery will nonetheless be documented.
Patients randomized to Group B will have their anti-TNFα therapy interrupted before surgery. There is no consensus on the optimal timing of anti-TNFα suspension before surgery. Many published guidelines suggest that the pharmacokinetics of the different anti-TNFα medications should be an important consideration in the perioperative management of these drugs. Different authors suggested that anti-TNFα therapies should be suspended between two and five half-lives prior to surgery. Similar timing was used in previous publications. In the current trial, anti-TNFα will be suspended three half-lives (± seven days) prior to surgery. All other medications used in the treatment of the disease (methotrexate, hydroxychloroquine, corticosteroid, etc.) will be documented and continued in the perioperative period. Non-steroidal anti-inflammatory drugs (NSAID) will be suspended seven days prior to surgery and will be restarted postoperatively. Anti-TNFα will be restarted once wound healing is completed.
Surgery
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female 18 years of age or older
- •Rheumatoid arthritis diagnostic according to the American College Rheumatology (ACR) 1987 criteria [38]
- •Patient treated with anti-TNFα for at least six months
- •Elective unilateral surgery of the foot and ankle
排除标准
- •Patient unable to give informed consent
- •Surgery on an infected site
- •Severe distal peripheral vascular disease (no distal pulse)
- •Medical condition contraindicating surgery
- •Patient treated with biologic DMARD other than anti-TNFα
- •Circumstances preventing an adequate postoperative follow-up
- •Revision surgery
研究组 & 干预措施
Anti-TNF suspended perioperatively
Patients randomized to Group B will have their anti-TNFα therapy interrupted before surgery. Different authors suggested that anti-TNFα therapies should be suspended between two and five half-lives prior to surgery. In the current trial, anti-TNFα will be suspended three half-lives (± seven days) prior to surgery. All other medications used in the treatment of the disease (methotrexate, hydroxychloroquine, corticosteroid, etc.) will be documented and continued in the perioperative period. Non-steroidal anti-inflammatory drugs (NSAID) will be suspended seven days prior to surgery and will be restarted postoperatively. Anti-TNFα will be restarted once wound healing is completed.
干预措施: Anti-TNF suspended perioperatively (Drug)
Anti-TNFα continued perioperatively
Patients randomized to Group A will continue their anti-TNFα treatment unaltered during the whole perioperative period. Surgery will be performed without consideration in regards to the timing of the treatment. The time elapsed between the last anti-TNFα administration and the surgery will nonetheless be documented.
干预措施: Anti-TNFα continued perioperatively (Drug)
结局指标
主要结局
Surgical site infection
时间窗: Within one year after surgery
Surgical site infection will be determined according to the definition of the Center for Disease Control (CDC).
次要结局
- Change in functional level(Until one year after surgery)
- Disease flare up(From the time the drug is suspended until one year after surgery)
- Poor wound healing(Within one year of surgery or until wound is completely healed)
- Reoperation rate(Within one year of surgery)
研究者
Mélissa Laflamme
MD, MSc, FRCSC, Orthopedic surgeon
CHU de Quebec-Universite Laval