Oral Flucloxacillin Alone Versus Flucloxacillin and Phenoxymethylpenicillin for the Emergency Department Outpatient Treatment of Cellulitis: a Non-inferiority Randomised Controlled Trial.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 414
- 试验地点
- 5
- 主要终点
- Investigator-determined clinical response
研究概览
简要总结
The main objective of this study is to investigate the non-inferiority of oral flucloxacillin alone compared with a combination of oral flucloxacillin and phenoxymethylpenicillin for the emergency department directed outpatient treatment of cellulitis, wound infections and abscesses, recently renamed by the Food and Drug Administration (FDA) as acute bacterial skin and skin structure infections (ABSSSIs). Half of the trial participants will receive flucloxacillin and placebo in combination, and the remaining half will be treated will flucloxacillin and phenoxymethylpenicillin.
In a secondary objective the trial aims to measure adherence and persistence of trial patients with outpatient antibiotic therapy. In addition a within-trial evaluation of the cost per quality adjusted life year (QALY) gained from the use of oral flucloxacillin compared with combination therapy from the perspective of the health-care payer (direct costs) the patient and government. Finally the study will externally validate the Extremity Soft Tissue Infection-score, a Health Related Quality of Life (HRQL) questionnaire designed to quantify the impact of cellulitis, wound infections and abscesses on patient HRQL in clinical trials.
详细描述
There is obvious clinical equipoise between the use of oral flucloxacillin alone or combined with phenoxymethylpenicillin for the emergency department treatment of cellulitis, wound infections and abscesses as evidenced by current disparate prescribing practice and hospital guidelines. Feasibility studies for the planned trial have shown that 45-50% of emergency department patients with these infections in Ireland are discharged on oral antibiotics which is consistent with findings in other jurisdictions. Despite the significant healthcare and economic costs associated with cellulitis, there is a paucity of scientific evidence concerning the appropriate antibiotic treatment for these conditions. Additionally, "less severe" infections tend to be over-treated and severe infections under-treated, indicating unjustifiable levels of antibiotic misuse, insufficient knowledge of therapeutics and a lack of evidence to risk-stratify patients with cellulitis to different treatments.The planned trial is therefore likely to be definitive due to the current clinical equipoise between the use of both penicillins for the emergency department outpatient treatment of this group of infections
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Clinically diagnosed cellulitis, wound infections or abscess (ABSSSI) affecting any body part, excluding the perineum, and having any two of the following signs:
- •Tenderness / Pain of affected area
- •Oedema / Induration
- •Regional lymphadenopathy
- •Cellulitis, wound infection and abscess deemed treatable with oral outpatient antibiotics in which either combination of antibiotic is likely to produce a clinical response (Eron Class 1-2)
- •Written informed consent obtained.
- •16 years of age or older.
- •Fluency in written and spoken English.
- •Willing to return for study follow-up or to have the research nurse visit their home.
- •Willing to receive a telephone call from a study investigator.
排除标准
- •Penicillin allergy (self-reported or confirmed).
- •Any cellulitis, wound infection and abscess that treating clinicians deem treatable with intravenous (IV) antibiotics.
- •Any cellulitis, wound infection and abscess that is more severe than Eron Class 2 (Appendix 2)
- •Any cellulitis, wound infection and abscess of the perineal region.
- •Patients who have received more than 24 hours of effective antibiotics for the current episode of acute cellulitis, wound infection or abscess
- •Any medical condition, based on clinical judgment, that may interfere with interpretation of the primary outcome measures (e.g. chronic skin condition at the lesion site)
- •Immunodeficiency from primary or secondary causes (e.g. corticosteroids, chemotherapeutic agents).
- •Previous history of renal dysfunction or known chronic kidney disease under care of a nephrologist. - Previous history of liver dysfunction defined as chronically deranged liver function tests elicited from medical notes or history.
- •Suspected or confirmed septic arthritis.
- •Suspected or confirmed osteomyelitis.
- •Infection involving prosthetic material.
- •Pregnant or lactating women.
- •Patients with a previous history of flucloxacillin- associated jaundice/hepatic dysfunction
- •Patients with a previous history of MRSA colonization/infection.
- •Patients with lactose intolerance diagnosed by a medical professional
研究组 & 干预措施
flucloxacillin + phenoxymethylpenicillin
Flucloxacillin 500 mg four times daily + Phenoxymethylpenicillin 500 mg four times daily for 7 days.
干预措施: Flucloxacillin (Drug)
flucloxacillin + phenoxymethylpenicillin
Flucloxacillin 500 mg four times daily + Phenoxymethylpenicillin 500 mg four times daily for 7 days.
干预措施: Phenoxymethylpenicillin (Drug)
flucloxacillin + placebo
Flucloxacillin 500 mg four times daily + Placebo four times daily for 7 days.
干预措施: Flucloxacillin (Drug)
flucloxacillin + placebo
Flucloxacillin 500 mg four times daily + Placebo four times daily for 7 days.
干预措施: Placebo (for phenoxymethylpenicillin) (Drug)
结局指标
主要结局
Investigator-determined clinical response
时间窗: Test Of Cure visit (Day 14-21 post randomization)
A trained member of the study team will determine clinical cure at the test of cure visit. This is a clinically-determined response to treatment based on the judgment of the trained member of the study team. Clinical cure will be defined as no treatment failure at any previous visit, and resolution or minimal presence of the erythema, swelling, tenderness, or induration from the baseline assessment, based on the study investigators clinical assessment
次要结局
- Early Clinical Response (ECR)(Day 2-3 post randomization)
- Clinical Treatment Failure(Up to 21 days post randomization)
- Adherence to Medication(End of Treatment (EOT) visit Day 8-10 post randomization)
- Adherence to medication using an electronic medication event monitoring system (MEMS®)(Day 2-3 and day 8-10 post randomization and initiation of therapy)
- Measurement of Health Related Quality of Life(Day 2-3 post-randomization, Day 8-10 post randomization, Day 14 -21 post randomization)
- Validation of the Extremity Soft Tissue Infections (ESTI)- score(Day 2-3 post-randomization, Day 8-10 post randomization, Day 14 -21 post randomization)
- Cost-effectiveness analysis(Day 14 - 21 post randomization)
- Measurement of Health Resource Use(Day 2-3 post-randomization, Day 8-10 post randomization, Day 14 -21 post randomization)