Penicillin for the Emergency Department Outpatient Treatment of CELLulitis (PEDOCELL)

Royal College of Surgeons, Ireland

Status and phase: Unknown; Phase 4

Conditions: Cellulitis; Wound Infection; Abscess

Treatments: Drug: Flucloxacillin; Drug: Phenoxymethylpenicillin; Drug: Placebo (for phenoxymethylpenicillin)

Study type: Interventional

Funder types: Other

Identifiers

NCT02922686

EudraCT Number: 2016-001528-69

HRB HRA Project ID (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 414 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Clinically diagnosed cellulitis, wound infections or abscess (ABSSSI) affecting any body part, excluding the perineum, and having any two of the following signs:

  • Erythema
  • Warmth
  • 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.

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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414 participants in 2 patient groups, including a placebo group

flucloxacillin + phenoxymethylpenicillin

Active Comparator group

Description:

Flucloxacillin 500 mg four times daily + Phenoxymethylpenicillin 500 mg four times daily for 7 days.

Treatment:

Drug: Phenoxymethylpenicillin

Drug: Flucloxacillin

flucloxacillin + placebo

Placebo Comparator group

Description:

Flucloxacillin 500 mg four times daily + Placebo four times daily for 7 days.

Treatment:

Drug: Placebo (for phenoxymethylpenicillin)

Drug: Flucloxacillin