Penicillin for the Emergency Department Outpatient Treatment of CELLulitis

NCT02922686 | Unknown Phase 4 DMC

• 2 other identifiers: EudraCT Number: 2016-001528-69HRB HRA Project ID
• Study Type: interventional
• Target: 414
• Locations: 1 country
• Sites: 5

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.

Conditions

Cellulitis; Wound Infection; Abscess

Outcome Measures

Primary Outcomes (1)

• Investigator-determined clinical response

  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

  Test Of Cure visit (Day 14-21 post randomization)

Secondary Outcomes (8)

• 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

Study Arms (2)

flucloxacillin + phenoxymethylpenicillin

ACTIVE COMPARATOR

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

Drug: Flucloxacillin; Drug: Phenoxymethylpenicillin

flucloxacillin + placebo

PLACEBO COMPARATOR

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

Drug: Flucloxacillin; Drug: Placebo (for phenoxymethylpenicillin)

Interventions

Flucloxacillin DRUG

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

Also known as: Floxapen, 500 mg Capsules,, Marketing Authorisation Number PA1380/011/002

flucloxacillin + phenoxymethylpenicillin; flucloxacillin + placebo

Phenoxymethylpenicillin DRUG

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

Also known as: Marketing Authorisation Number PL; 04520/0005

flucloxacillin + phenoxymethylpenicillin

Placebo (for phenoxymethylpenicillin) 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

Also known as: Over-encapsulated investigative medicinal product.

flucloxacillin + placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Royal College of Surgeons, Ireland: lead
• Health Research Board, Ireland: collaborator

Study Sites (5)

Department of Emergency Medicine, Connolly Hospital,

Blanchardstown, Dublin, Dublin 15, Ireland

Location

Department of Emergency Medicine, Mater Misericordiae University Hospital

Dublin, Dublin, Dublin 7, Ireland

Location

Beaumont Hospital,

Dublin, Dublin, Dublin 9, Ireland

Location

Department of Emergency Medicine, Mercy University Cork

Cork, Greenville Place, Cork, Ireland

Location

Department of Emergency Medicine, Cork University Hospital

Cork, Wilton, Cork, Ireland

Location

Related Publications (6)

• 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.

  PMID: 25556256 BACKGROUND

• 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.

  PMID: 11698996 BACKGROUND

• 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.

  PMID: 20556757 BACKGROUND

• 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.

  PMID: 17034641 BACKGROUND

• 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.

  PMID: 23542420 BACKGROUND

• 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.

  PMID: 28836993 DERIVED

MeSH Terms

Conditions

Cellulitis; Wound Infection; Abscess

Interventions

Floxacillin; Penicillin V

Condition Hierarchy (Ancestors)

Skin Diseases, Infectious; Infections; Suppuration; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cloxacillin; Oxacillin; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Adrian Moughty

  Mater Misericordiae University Hospital

  PRINCIPAL INVESTIGATOR

• Joseph McKeever

  Connolly Hospital Blanchardstown

  PRINCIPAL INVESTIGATOR

• Conor Deasy

  Department of Emergency Medicine, Cork University Hopsital, Cork

  PRINCIPAL INVESTIGATOR

• Chris Luke

  Department of Emergency Medicine, Mercy University, Cork

  PRINCIPAL INVESTIGATOR

• Abel Wakai, MD FRCEM

  Department of Emergency Medicine, Beaumont Hospital, Dublin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abel Wakai, MD FRCEM

CONTACT

003531 8093000; awakai@rcsi.ie

Michael Quirke, MB FRCEM

CONTACT

00353 1 8093000; michaelquirke@rcsi.ie

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2016
• First Posted: October 4, 2016
• Study Start: December 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: October 4, 2016

Record last verified: 2016-07

Locations

IE (5)