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

Primary Purpose

Cellulitis, Wound Infection, Abscess

Status

Unknown status

Phase

Phase 4

Locations

Ireland

Study Type

Interventional

Intervention

Flucloxacillin

Phenoxymethylpenicillin

Placebo (for phenoxymethylpenicillin)

About this trial

This is an interventional treatment trial for Cellulitis

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesAccepts 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

Sites / Locations

Department of Emergency Medicine, Connolly Hospital,
Department of Emergency Medicine, Mercy University Cork
Department of Emergency Medicine, Cork University Hospital
Department of Emergency Medicine, Mater Misericordiae University Hospital
Beaumont Hospital,

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

flucloxacillin + phenoxymethylpenicillin

flucloxacillin + placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Early Clinical Response (ECR)

Early clinical response is defined as greater than or equal to a 20% reduction in the lesion surface area from that which was measured at enrolment.

Clinical Treatment Failure

Any patient outcome designated as a clinical treatment failure at any time before and including the test of cure visit, will be categorized as a treatment failure. This commences with the early clinical response visit and includes serial changes in the surface area of the cellulitis lesion (erythema, oedema, tenderness and induration), clinical assessment of progress and health related quality of life measurements.

Adherence to Medication

Medication adherence will be measured by counting the number of unused study medication at the end of treatment visit

Adherence to medication using an electronic medication event monitoring system (MEMS®)

A specific sub-study will be performed measuring adherence and persistence to antibiotic treatment using a MEMS® cap. The cap will be fitted to the dispensed medication bottle. MEMS® caps will be returned with the clinical trials supplies on the follow up visits.medication at the end of treatment visit

Measurement of Health Related Quality of Life

The EuroQol (EQ-5D-5L) will be used to obtain patient reports of health related quality of life and used in the estimation of quality adjusted life years.

Validation of the Extremity Soft Tissue Infections (ESTI)- score

The ESTI will be used to obtain patient reports of health related quality of life and will be mapped on to EQ-5D-5L levels, to assess the accuracy of ESTI for use in cost-effectiveness studies

Cost-effectiveness analysis

Analysis will consist of a within-trial evaluation of the cost QALY for oral flucloxacillin compared with oral flucloxacillin and phenoxymethylpenicillin over a one month time horizon from the perspective of the healthcare payer, the patient and the government. The CE analysis will use resource use data, where costs will be assigned to derive cost and will also use the QALY derived from the EQ5D-5L, to give overall cost per QALY.

Measurement of Health Resource Use

A health economics resource utilization tool is being constructed to collect data on resource use, e.g. direct costs- hospital visits, primary care visits, and indirect costs such as transport and lost work productivity.

Full Information

NCT ID

NCT02922686

First Posted

August 9, 2016

Last Updated

September 30, 2016

Sponsor

Royal College of Surgeons, Ireland

Collaborators

Health Research Board, Ireland

1. Study Identification

Unique Protocol Identification Number

NCT02922686

Brief Title

Penicillin for the Emergency Department Outpatient Treatment of CELLulitis

Acronym

PEDOCELL

Official Title

Oral Flucloxacillin Alone Versus Flucloxacillin and Phenoxymethylpenicillin for the Emergency Department Outpatient Treatment of Cellulitis: a Non-inferiority Randomised Controlled Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Unknown status

Study Start Date

December 2016 (undefined)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Royal College of Surgeons, Ireland

Collaborators

Health Research Board, Ireland

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cellulitis, Wound Infection, Abscess

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

414 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

flucloxacillin + phenoxymethylpenicillin

Arm Type

Active Comparator

Arm Description

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

Arm Title

flucloxacillin + placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Flucloxacillin

Other Intervention Name(s)

Floxapen, 500 mg Capsules,, Marketing Authorisation Number PA1380/011/002

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Phenoxymethylpenicillin

Other Intervention Name(s)

Marketing Authorisation Number PL; 04520/0005

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo (for phenoxymethylpenicillin)

Other Intervention Name(s)

Over-encapsulated investigative medicinal product.

Intervention Description

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

Primary Outcome Measure Information:

Title

Investigator-determined clinical response

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Early Clinical Response (ECR)

Description

Early clinical response is defined as greater than or equal to a 20% reduction in the lesion surface area from that which was measured at enrolment.

Time Frame

Day 2-3 post randomization

Title

Clinical Treatment Failure

Description

Time Frame

Up to 21 days post randomization

Title

Adherence to Medication

Description

Medication adherence will be measured by counting the number of unused study medication at the end of treatment visit

Time Frame

End of Treatment (EOT) visit Day 8-10 post randomization

Title

Adherence to medication using an electronic medication event monitoring system (MEMS®)

Description

Time Frame

Day 2-3 and day 8-10 post randomization and initiation of therapy

Title

Measurement of Health Related Quality of Life

Description

The EuroQol (EQ-5D-5L) will be used to obtain patient reports of health related quality of life and used in the estimation of quality adjusted life years.

Time Frame

Day 2-3 post-randomization, Day 8-10 post randomization, Day 14 -21 post randomization

Title

Validation of the Extremity Soft Tissue Infections (ESTI)- score

Description

The ESTI will be used to obtain patient reports of health related quality of life and will be mapped on to EQ-5D-5L levels, to assess the accuracy of ESTI for use in cost-effectiveness studies

Time Frame

Day 2-3 post-randomization, Day 8-10 post randomization, Day 14 -21 post randomization

Title

Cost-effectiveness analysis

Description

Time Frame

Day 14 - 21 post randomization

Title

Measurement of Health Resource Use

Description

Time Frame

Day 2-3 post-randomization, Day 8-10 post randomization, Day 14 -21 post randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Abel Wakai, MD FRCEM

Phone

003531 8093000

awakai@rcsi.ie

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Quirke, MB FRCEM

Phone

00353 1 8093000

michaelquirke@rcsi.ie

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adrian Moughty

Organizational Affiliation

Mater Misericordiae University Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Joseph McKeever

Organizational Affiliation

Connolly Hospital Blanchardstown

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Conor Deasy

Organizational Affiliation

Department of Emergency Medicine, Cork University Hopsital, Cork

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Chris Luke

Organizational Affiliation

Department of Emergency Medicine, Mercy University, Cork

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Abel Wakai, MD FRCEM

Organizational Affiliation

Department of Emergency Medicine, Beaumont Hospital, Dublin

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Emergency Medicine, Connolly Hospital,

City

Blanchardstown

State/Province

Dublin

ZIP/Postal Code

Dublin 15

Country

Ireland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joseph McKeever

joseph.mckeever@hse.ie

Facility Name

Department of Emergency Medicine, Mercy University Cork

City

Cork

State/Province

Greenville Place

ZIP/Postal Code

Cork

Country

Ireland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chris Luke

Facility Name

Department of Emergency Medicine, Cork University Hospital

City

Cork

State/Province

Wilton

ZIP/Postal Code

Cork

Country

Ireland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Conor Deasy

conor.deasy@hse.ie

Facility Name

Department of Emergency Medicine, Mater Misericordiae University Hospital

City

Dublin

ZIP/Postal Code

Dublin 7

Country

Ireland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Adrian Moughty

amoughty@mater.ie

First Name & Middle Initial & Last Name & Degree

Michael Quirke

Facility Name

Beaumont Hospital,

City

Dublin

ZIP/Postal Code

Dublin 9

Country

Ireland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Abel Wakai, MD FRCEM

awakai@rcsi.ie

First Name & Middle Initial & Last Name & Degree

Michael Quirke

michaelquirke@rcsi.ie

First Name & Middle Initial & Last Name & Degree

Abel Wakai, MD FRCEM

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

25556256

Citation

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.

Results Reference

background

PubMed Identifier

11698996

Citation

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.

Results Reference

background

PubMed Identifier

20556757

Citation

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.

Results Reference

background

PubMed Identifier

17034641

Citation

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.

Results Reference

background

PubMed Identifier

23542420

Citation

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.

Results Reference

background

PubMed Identifier

28836993

Citation

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.

Results Reference

derived

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Penicillin for the Emergency Department Outpatient Treatment of CELLulitis

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