Penicillin for the Emergency Department Outpatient Treatment of CELLulitis

NCT ID: NCT02922686

Last Updated: 2016-10-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 414 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2019-12-31

Brief Summary

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.

Detailed 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

Conditions

Cellulitis; Wound Infection; Abscess

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

flucloxacillin + phenoxymethylpenicillin

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

Group Type: ACTIVE_COMPARATOR

Flucloxacillin

Intervention Type: DRUG

One flucloxacillin capsule of 500mg strength taken four times daily for 7 days

Phenoxymethylpenicillin

Intervention Type: DRUG

One capsule of phenoxymethylpenicillin of 500 mg strength taken four times daily for 7 days

flucloxacillin + placebo

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

Group Type: PLACEBO_COMPARATOR

Flucloxacillin

Intervention Type: DRUG

One flucloxacillin capsule of 500mg strength taken four times daily for 7 days

Placebo (for phenoxymethylpenicillin)

Intervention Type: DRUG

Over-encapsulation of phenoxymethylpenicillin will be performed by the manufacturer of the investigational medicinal products such that placebo and active phenoxymethylpenicillin are identical in size, shape, colour and smell, and are packaged in identical bottles

Interventions

Flucloxacillin

One flucloxacillin capsule of 500mg strength taken four times daily for 7 days

Intervention Type: DRUG

Phenoxymethylpenicillin

One capsule of phenoxymethylpenicillin of 500 mg strength taken four times daily for 7 days

Intervention Type: DRUG

Placebo (for phenoxymethylpenicillin)

Over-encapsulation of phenoxymethylpenicillin will be performed by the manufacturer of the investigational medicinal products such that placebo and active phenoxymethylpenicillin are identical in size, shape, colour and smell, and are packaged in identical bottles

Intervention Type: DRUG

Other Intervention Names

Floxapen, 500 mg Capsules,; Marketing Authorisation Number PA1380/011/002; Marketing Authorisation Number PL; 04520/0005; Over-encapsulated investigative medicinal product.

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Health Research Board, Ireland

OTHER

Sponsor Role: collaborator

Royal College of Surgeons, Ireland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adrian Moughty

Role: PRINCIPAL_INVESTIGATOR

Mater Misericordiae University Hospital

Joseph McKeever

Role: PRINCIPAL_INVESTIGATOR

Connolly Hospital Blanchardstown

Conor Deasy

Role: PRINCIPAL_INVESTIGATOR

Department of Emergency Medicine, Cork University Hopsital, Cork

Chris Luke

Role: PRINCIPAL_INVESTIGATOR

Department of Emergency Medicine, Mercy University, Cork

Abel Wakai, MD FRCEM

Role: PRINCIPAL_INVESTIGATOR

Department of Emergency Medicine, Beaumont Hospital, Dublin

Locations

Department of Emergency Medicine, Connolly Hospital,

Blanchardstown, Dublin, Ireland

Department of Emergency Medicine, Mater Misericordiae University Hospital

Dublin, Dublin, Ireland

Beaumont Hospital,

Dublin, Dublin, Ireland

Department of Emergency Medicine, Mercy University Cork

Cork, Greenville Place, Ireland

Department of Emergency Medicine, Cork University Hospital

Cork, Wilton, Ireland

Countries

Ireland

Central Contacts

Abel Wakai, MD FRCEM

Role: CONTACT

awakai@rcsi.ie

003531 8093000

Michael Quirke, MB FRCEM

Role: CONTACT

michaelquirke@rcsi.ie

00353 1 8093000

Facility Contacts

Joseph McKeever

Role: primary

joseph.mckeever@hse.ie

Adrian Moughty

Role: primary

amoughty@mater.ie

Michael Quirke

Role: backup

Abel Wakai, MD FRCEM

Role: primary

awakai@rcsi.ie

Michael Quirke

Role: backup

michaelquirke@rcsi.ie

Chris Luke

Role: primary

Conor Deasy

Role: primary

conor.deasy@hse.ie

References

Quirke M, Saunders J, O'Sullivan R, Milenkovski H, Wakai A. A pilot cross-sectional study of patients presenting with cellulitis to emergency departments. Ir Med J. 2014 Nov-Dec;107(10):316-8.

Reference Type: BACKGROUND

PMID: 25556256 (View on PubMed)

Dong SL, Kelly KD, Oland RC, Holroyd BR, Rowe BH. ED management of cellulitis: a review of five urban centers. Am J Emerg Med. 2001 Nov;19(7):535-40. doi: 10.1053/ajem.2001.28330.

Reference Type: BACKGROUND

PMID: 11698996 (View on PubMed)

Kilburn SA, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev. 2010 Jun 16;2010(6):CD004299. doi: 10.1002/14651858.CD004299.pub2.

Reference Type: BACKGROUND

PMID: 20556757 (View on PubMed)

Storck AJ, Laupland KB, Read RR, Mah MW, Gill JM, Nevett D, Louie TJ. Development of a Health-Related Quality of Life Questionnaire (HRQL) for patients with Extremity Soft Tissue Infections (ESTI). BMC Infect Dis. 2006 Oct 11;6:148. doi: 10.1186/1471-2334-6-148.

Reference Type: BACKGROUND

PMID: 17034641 (View on PubMed)

Quirke M, O'Sullivan R, McCabe A, Ahmed J, Wakai A. Are two penicillins better than one? A systematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis. Eur J Emerg Med. 2014 Jun;21(3):170-4. doi: 10.1097/MEJ.0b013e328360d980.

Reference Type: BACKGROUND

PMID: 23542420 (View on PubMed)

Boland F, Quirke M, Gannon B, Plunkett S, Hayden J, McCourt J, O'Sullivan R, Eustace J, Deasy C, Wakai A. The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial: update to the study protocol and detailed statistical analysis plan (SAP). Trials. 2017 Aug 24;18(1):391. doi: 10.1186/s13063-017-2121-2.

Reference Type: DERIVED

PMID: 28836993 (View on PubMed)

Other Identifiers

HRB HRA Project ID

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EudraCT Number: 2016-001528-69

Identifier Type: -

Identifier Source: org_study_id