The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial: Update to the study protocol and detailed statistical analysis plan (SAP)

Fiona Boland, Michael Quirke, Brenda Gannon, Sinead Plunkett, John Hayden, John McCourt, Ronan O'Sullivan, Joseph Eustace, Conor Deasy, Abel Wakai

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Methods/design: Patients will be randomised to either orally administered flucloxacillin 500mg four times daily and placebo or orally administered 500mg of flucloxacillin four times daily and phenoxymethylpenicillin 500mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias. Trial registration: EU Clinical Trials Register (EudraCT number: 2016-001528-69). Registered on 5 April 2016. ClinicalTrials.gov, ID: NCT02922686. Registered on 9 August 2016.

Original languageEnglish
Article number391
JournalTrials
Volume18
Issue number1
DOIs
Publication statusPublished - 24 Aug 2017
Externally publishedYes

Keywords

  • Abscess
  • Cellulitis
  • Emergency department
  • Flucloxacillin
  • Phenoxymethylpenicillin
  • Randomised controlled trial
  • Statistical analysis plan
  • Wound infection

Cite this

Boland, Fiona ; Quirke, Michael ; Gannon, Brenda ; Plunkett, Sinead ; Hayden, John ; McCourt, John ; O'Sullivan, Ronan ; Eustace, Joseph ; Deasy, Conor ; Wakai, Abel. / The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial : Update to the study protocol and detailed statistical analysis plan (SAP). In: Trials. 2017 ; Vol. 18, No. 1.
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abstract = "Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Methods/design: Patients will be randomised to either orally administered flucloxacillin 500mg four times daily and placebo or orally administered 500mg of flucloxacillin four times daily and phenoxymethylpenicillin 500mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias. Trial registration: EU Clinical Trials Register (EudraCT number: 2016-001528-69). Registered on 5 April 2016. ClinicalTrials.gov, ID: NCT02922686. Registered on 9 August 2016.",
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The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial : Update to the study protocol and detailed statistical analysis plan (SAP). / Boland, Fiona; Quirke, Michael; Gannon, Brenda; Plunkett, Sinead; Hayden, John; McCourt, John; O'Sullivan, Ronan; Eustace, Joseph; Deasy, Conor; Wakai, Abel.

In: Trials, Vol. 18, No. 1, 391, 24.08.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial

T2 - Update to the study protocol and detailed statistical analysis plan (SAP)

AU - Boland, Fiona

AU - Quirke, Michael

AU - Gannon, Brenda

AU - Plunkett, Sinead

AU - Hayden, John

AU - McCourt, John

AU - O'Sullivan, Ronan

AU - Eustace, Joseph

AU - Deasy, Conor

AU - Wakai, Abel

PY - 2017/8/24

Y1 - 2017/8/24

N2 - Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Methods/design: Patients will be randomised to either orally administered flucloxacillin 500mg four times daily and placebo or orally administered 500mg of flucloxacillin four times daily and phenoxymethylpenicillin 500mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias. Trial registration: EU Clinical Trials Register (EudraCT number: 2016-001528-69). Registered on 5 April 2016. ClinicalTrials.gov, ID: NCT02922686. Registered on 9 August 2016.

AB - Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Methods/design: Patients will be randomised to either orally administered flucloxacillin 500mg four times daily and placebo or orally administered 500mg of flucloxacillin four times daily and phenoxymethylpenicillin 500mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias. Trial registration: EU Clinical Trials Register (EudraCT number: 2016-001528-69). Registered on 5 April 2016. ClinicalTrials.gov, ID: NCT02922686. Registered on 9 August 2016.

KW - Abscess

KW - Cellulitis

KW - Emergency department

KW - Flucloxacillin

KW - Phenoxymethylpenicillin

KW - Randomised controlled trial

KW - Statistical analysis plan

KW - Wound infection

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U2 - 10.1186/s13063-017-2121-2

DO - 10.1186/s13063-017-2121-2

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JF - Trials

SN - 1745-6215

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