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Trial registered on ANZCTR


Registration number
ACTRN12619000407190
Ethics application status
Approved
Date submitted
20/02/2019
Date registered
13/03/2019
Date last updated
17/10/2019
Date data sharing statement initially provided
13/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing short versus long courses of intravenous antibiotics for diabetic foot infection
Scientific title
Comparison of the effect of an early transition to oral versus prolonged intravenous antibiotic treatment strategy on clinical outcomes in residual osteomyelitis post surgical debridement in diabetic foot infections: a randomised open-label pilot study
Secondary ID [1] 297464 0
None
Universal Trial Number (UTN)
U1111-1228-9791
Trial acronym
PIVETO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic foot infection 311654 0
Osteomyelitis 311655 0
Condition category
Condition code
Infection 310275 310275 0 0
Other infectious diseases
Metabolic and Endocrine 310276 310276 0 0
Diabetes
Musculoskeletal 310307 310307 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Early Transition to Orals: Participants randomised to the experimental arm will receive at least one but no more than seven days (from start of current treatment course) of intravenous antibiotics before transitioning to an oral antibiotic regime. The antibiotic agent(s), dose(s) and duration will be individually selected by an Infectious Disease specialist for each participant.
Intervention adherence will be assessed by use of the Brief Medication Questionnaire at week 3-4 after start of treatment with a target of >80% of prescribed doses.
Intervention code [1] 313719 0
Treatment: Drugs
Comparator / control treatment
Prolonged Intravenous Therapy: Participants randomised to the control arm will receive current standard of care with at least four weeks of intravenous antibiotics (from start of current treatment course) before transitioning to an oral antibiotic regime. The antibiotic agent(s), dose(s) and duration will be individually selected by an Infectious Disease specialist for each participant.
Control group
Active

Outcomes
Primary outcome [1] 319170 0
Diagnosis of definite osteomyelitis at the amputation site as per 2008 IWGDF consensus definition (modified to include radionuclide imaging and to exclude localised clinical signs of infection treated as a superficial wound infection with an antibiotic for < 1 week) by the blinded endpoint review committee. The committee will determine by consensus the osteomyelitis diagnostic category (definite, probable, possible or unlikely) by reviewing study data redacted for any information that may betray treatment allocation.
Timepoint [1] 319170 0
Six months from start of treatment
Primary outcome [2] 319172 0
Complete healing of the amputation site at 6 months as defined by full epithelialisation, after debridement of callus, lasting for at least 2 weeks. Primary outcome arbitration at the interim analysis and at the final analysis will be performed using the database, wound dimension and clinical images by two independent senior clinicians blinded (not investigators) to the intervention.
Timepoint [2] 319172 0
Six months from start of treatment
Secondary outcome [1] 367168 0
Wound healing trajectory (percentage change in ulcer wound dimensions) using a validated digital wound measurement tool (Silhouette or Visitrak)
Timepoint [1] 367168 0
Six months from start of treatment
Secondary outcome [2] 367171 0
Quality of Life (EQ-5D)
Timepoint [2] 367171 0
Three months and six months from start of treatment
Secondary outcome [3] 367178 0
Proportion with adverse events including classification of severity and relatedness to intervention as determined by a senior medical investigator
- Re-admissions for inpatient care
- Minor amputation at index or other site
- Major amputation at index or other site
- Line-related complications (infection, thrombosis, mechanical)
- Antibiotic related adverse events requiring interruption or cessation of treatment
Timepoint [3] 367178 0
Six months from start of treatment
Secondary outcome [4] 368092 0
Probable or possible osteomyelitis at the amputation site as per 2008 IWGDF consensus definition (modified to include radionuclide imaging and to exclude localised clinical signs of infection treated as a superficial wound infection with an antibiotic for < 1 week) by the blinded endpoint review committee. The committee will determine by consensus the osteomyelitis diagnostic category (definite, probable, possible or unlikely) by reviewing study data redacted for any information that may betray treatment allocation.
Timepoint [4] 368092 0
Six months from start of treatment
Secondary outcome [5] 368094 0
Antibiotic free days as per recorded prescription data
Timepoint [5] 368094 0
Six months from start of treatment

Eligibility
Key inclusion criteria
Adult inpatients requiring surgical management for diabetic foot infection
Positive bone chip (culture or microscopy) post-surgical procedure or negative bone chip (culture or microscopy)with high clinical suspicion for a residual osteomyelitis
Type 1 or 2 diabetes mellitus
Infection below ankle
Likely to be able to be followed at health facility for subsequent six months
Has received 7 days or less of intravenous therapy since admission to the hospital
Is willing and able to give informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with toe pressure < 30mmHg despite revascularisation
An infection for which (as per ID Physician’s opinion) there are no suitable antibiotic choices to permit randomisation between the two arms of the trial (for example, where organisms are only sensitive to intravenous antibiotics)
Systemic sepsis (eg. hypotension requiring inotropic support, blood cultures positive for Staphylococcus aureus) or other indications that mandate prolonged intravenous antibiotics
Significant restricted therapeutic options (to either intravenous or oral antibiotics alone) because of patient or microbiological factors (eg. allergy, drug resistance)
Pregnant women

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer after enrolment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A permuted block randomisation method will be used with random variable block sizes.
1:1 with no stratification.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Baseline characteristics of the patients in the treatment groups will be described using summary statistics, with transformation of non-normally distributed data where appropriate. Treatment effects on categorical and continuous endpoints will be compared using logistic regression analysis and general linear modelling, with adjustment for baseline covariates and time to treatment failure event will be compared using Cox proportional hazards regression analysis. The efficacy of the treatment strategies will be compared using both intention to treat and per protocol analyses.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 13211 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 25768 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 302034 0
Charities/Societies/Foundations
Name [1] 302034 0
RPH Medical Research Foundation
Address [1] 302034 0
PO Box 2323, East Perth WA 6892
Country [1] 302034 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
Royal Perth Hospital, 197 Wellington St, Perth WA 6000
Country
Australia
Secondary sponsor category [1] 301836 0
None
Name [1] 301836 0
Address [1] 301836 0
Country [1] 301836 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302717 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 302717 0
197 Wellington Street
Perth Western Australia 6000
Ethics committee country [1] 302717 0
Australia
Date submitted for ethics approval [1] 302717 0
18/06/2018
Approval date [1] 302717 0
07/12/2018
Ethics approval number [1] 302717 0
RGS959

Summary
Brief summary
In patients with diabetes, foot ulceration and infection occur commonly, and are associated with significant morbidity and use of health service resources. Diabetic foot infections are usually associated with ulcers, and can spread from the soft tissue to involve underlying bone (osteomyelitis). Diabetic foot infection with osteomyelitis (DFO) is associated with delayed ulcer healing and increased risk of amputation.

Current guidelines for treatment of osteomyelitis include a prolonged course (4–6 weeks) of intravenous antibiotics, However, this requires hospital admission and/or use of ambulatory care nursing services, as well as establishment of intravenous access for the duration of therapy, all of which place considerable burden on health services and the individual patient. Also, the antibiotic-related costs are much higher than oral therapy. Despite this, there is no evidence to suggest that oral therapy results in inferior outcomes.

We hypothesise that, the use of oral antibiotics, particularly agents with high bioavailability, good tissue penetration and activity against the known or likely pathogens, might be effective and potentially less costly than intravenous therapy for DFO.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91142 0
Dr Edward Raby
Address 91142 0
Department of Infectious Diseases
Royal Perth Hospital
197 Wellington St, Perth WA 6000
Country 91142 0
Australia
Phone 91142 0
+61 8 92242244
Fax 91142 0
Email 91142 0
edward.raby@health.wa.gov.au
Contact person for public queries
Name 91143 0
Dr Edward Raby
Address 91143 0
Department of Infectious Diseases
Royal Perth Hospital
197 Wellington St, Perth WA 6000
Country 91143 0
Australia
Phone 91143 0
+61 8 92242244
Fax 91143 0
Email 91143 0
edward.raby@health.wa.gov.au
Contact person for scientific queries
Name 91144 0
Dr Edward Raby
Address 91144 0
Department of Infectious Diseases
Royal Perth Hospital
197 Wellington St, Perth WA 6000
Country 91144 0
Australia
Phone 91144 0
+61 8 92242244
Fax 91144 0
Email 91144 0
edward.raby@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Unclear if sharing permitted through current HREC approval
What supporting documents are/will be available?
No other documents available
Summary results
No Results