Randomized Trial to Assess PO Versus IV Antibiotics (POvIV)

• ClinicalTrials.gov Identifier: NCT01714596
• Recruitment Status: Completed
• First Posted: October 26, 2012
• Last Update Posted: February 11, 2021
• Sponsor: Major Extremity Trauma Research Consortium
• Information provided by (Responsible Party): Major Extremity Trauma Research Consortium

Tracking Information

• First Submitted Date: April 30, 2012
• First Posted Date: October 26, 2012
• Last Update Posted Date: February 11, 2021
• Actual Study Start Date: December 3, 2013
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 1, 2021): Study injury related surgical interventions by 1 year [ Time Frame: 1 year ]

Original Primary Outcome Measures (submitted: October 25, 2012)

Primary objective: investigate the efficacy of oral (PO) antibiotic therapy versus intravenous (IV) antibiotics in the treatment of acute infection after plate fixation of fractures. [ Time Frame: 4 Years ]

Phase III randomized controlled clinical trial to investigate efficacy of PO vs. IV antibiotics in the treatment of early (<6 weeks) post-operative wound infections. Clinical efficacy will be measured by the incidence of treatment failure within the first one-year of follow-up as defined by culture positive recurrence of infection prior to bony union, progressive radiographic plate loosening, joint erosion due to infection that results in amputation or joint fusion, development of adverse reactions to antibiotics that cause change in form of administration.

Current Secondary Outcome Measures (submitted: February 8, 2021)

• Treatment Failure by 1 year [ Time Frame: 1 year ]
  Treatment failure is defined as wound problems that require surgery >2 weeks after initial debridement, infection recurrence, infection with a new pathogen, joint erosion, implant failure, medical problems related to the treatment administration which necessitates a switch from one arm to the other.
• Re-hospitalizations by 1 year [ Time Frame: 1 year ]
  Re-hospitalization for complications, such as infection, non-union and amputation
• Healthcare costs [ Time Frame: 1 year ]
  Cost of PO versus IV medications include medical record and bill abstracted costs associated with outpatient clinic visits, home health visits, medication, subsequent hospital readmission, and other types of medical care as identified over the course of the study.
• Medication Adherence [ Time Frame: 1 year ]
  Patient adherence to PO and IV medications Patient adherence with PO antibiotics will be monitored through wireless-enabled microchip monitors embedded in pill bottles by the Medication Event Monitoring System (MEMS) and weekly adherence questionnaire.
• Satisfaction with treatment [ Time Frame: 1 year ]
  Patient satisfaction with treatment measured by Short Form Patient Satisfaction Questionnaire (PSQ-18) The PSQ-18 measures 6 domains: technical quality, interpersonal manner, communication, financial aspects of care, time spent with doctor, and accessibility. A score of 0.8 or higher in each domain correlates with improved satisfaction.

Original Secondary Outcome Measures (submitted: October 25, 2012)

Patient Adherence [ Time Frame: 4 Years ]

Patient adherence with PO antibiotics will be monitored through wireless-enabled microchip monitors embedded in pill bottles. The Home Health agency administering the IV antibiotics will be contacted to assess adherence with IV antibiotic regimen by assessing utilization of supplied antibiotics.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Randomized Trial to Assess PO Versus IV Antibiotics
• Official Title: A Prospective Randomized Trial to Assess PO Versus IV Antibiotics for the Treatment of Post-op Wound Infection After Extremity Fractures (POvIV)

Brief Summary

The goal of this study is to evaluate the effect of treatment of post-op wound infection in long bones after fracture fixation or joint fusion and either: (Group 1) operative debridement and PO antibiotic treatment for 6 weeks; or (Group 2) operative debridement and IV antibiotics for 6 weeks.

Primary Hypothesis 1: The rate of study injury related surgical interventions by one year in Group 1 will be non-inferior to the rate in Group 2.

Secondary Hypothesis 1: The rate of treatment failure by one year in Group 1 will be non-inferior to the rate in Group 2. Treatment failure is defined as wound problems that require surgery >2 weeks after initial debridement, infection recurrence, infection with a new pathogen, joint erosion, implant failure, medical problems related to the treatment administration which necessitates a switch from one arm to the other.

Secondary Hypothesis 2: The rate of re-hospitalization for complications, infection, non-union and amputation by one year in Group 1 will be non-inferior to the rate in Group 2.

Secondary Hypothesis 3: Following discharge for treatment of infection, per patient treatment costs at 1 year will be lower in Group 1 than in Group 2.

Secondary Hypothesis 4: Adherence in Group 1 will be non-inferior to adherence in Group 2.

Secondary Hypothesis 5: Patient satisfaction with treatment in Group 1 will be non-inferior to adherence in Group 2.

Specific Aim 2: To build and validate a risk prediction model for failure of treatment of early post-op wound infections after fixation of fractures and joint fusions.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Wound Infection

Intervention

Other: PO versus IV antibiotics Route of administration evaluation

This is a study of oral (per os, (PO)) antibiotic therapy versus intravenous (IV) antibiotics in the treatment of acute infection after fixation of fractures and joint fusions. This is not a study of an experimental drug but a study of route of administration of standard use antibiotics. Antibiotic regimen options decision will be made by the Study Surgeon at each site in consult with local Infectious Disease experts based on local standard practices and bacterial susceptibilities.

Other Name: based on local practices and bacterial susceptibilities

Study Arms

• Active Comparator: Oral Antibiotic
  Oral Antibiotic Arm; Participants assigned to this group will receive oral antibiotics as prescribed by their treating physician.
  Intervention: Other: PO versus IV antibiotics Route of administration evaluation
• Active Comparator: IV Antibiotic
  Participants assigned to this group will receive intravenous (IV) antibiotics as prescribed by their treating physician.
  Intervention: Other: PO versus IV antibiotics Route of administration evaluation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2021): 233
• Original Estimated Enrollment (submitted: October 25, 2012): 600
• Actual Study Completion Date: December 30, 2020
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with any fractures of any bone at or proximal to and including the tarsal/metatarsal joint (Lisfranc) or proximal to the carpal joints (includes distal radius fractures), excluding the spine, treated with any type of internal fixation, or
2. Patients undergoing fusion of any bone at or proximal to and including the subtalar joint or radial carpal joint, (excluding the spine) that develop a post op wound infection at any time.

3. Patients diagnosed with a wound infection of the study injury, defined as patients with at least one of the following:

   1. Deep culture positive after operative debridement.
   2. Cultures positive in thio only after operative debridement.
   3. Negative culture after operative debridement if wound infection meets the Center for Disease control and Prevention (CDC) criteria.
4. Patients who are English or Spanish competent.
5. Patients aged 18 - 84.
6. Patients with bacteria susceptible to both PO and IV antibiotics.
7. Patients able to be treated for their infection at the METRC facility for at least 12 months following definitive surgical procedure
8. Patients may have multiple eligible study-eligible injuries.
9. Patients may have temporary external fixation prior to definitive fixation.
10. Patients may have received antibiotics prior to operative wound debridement.
11. Patient is able to obtain study medication(s).
12. Patient may be pregnant at the time of screening.

Exclusion Criteria:

1. Patients who have high risk of amputation of the study limb (based on opinion of the initial managing physician).
2. Patients undergoing treatment with any other investigational therapy within the month preceding implantation or planned within the 12 months following implantation.

3. Patients with history of chronic infection at the site of study injury, defined as:

   patients with chronic osteomyelitis identified by radiographic erosion or sequestrum; or patients with more than one instance of surgical treatment of infection and approximately 6 week course of antibiotics.

4. Patients with pathological fractures; a known history of Paget's disease.
5. Patients for whom the definitive treatment of the study injury was an external fixator.
6. Patients who are currently on Selective Serotonin Reuptake Inhibitor (SSRI) medication (e.g. Zoloft, Prozac, Celexa), and bacteria is MRSA
7. Patients with cultures positive in thio only.
8. Patients who are incarcerated or who have unstable housing situations due to concerns regarding ability to receive home care, adherence phone calls, and maintain follow up. .
9. Patients or designated proxy who are unwilling to provide consent.
10. Patients with a history of IV drug use who in the investigator's opinion are unsuitable candidates for IV therapy.
11. Patients likely to have severe problems maintaining follow-up, including patients diagnosed with a severe psychiatric conditions, patients who live too far outside the hospital's catchment area.
12. Patients with traumatic brain injury or who are intellectually challenged and who lack adequate family support to ensure adherence to the protocol.
13. Patients unable to swallow oral medications or without adequately functioning GI tract.
14. Patients who, based upon the clinical judgment of the treating clinician, are NOT equally suited for treatment with either oral or intravenous antibiotics (i.e., those for whom there is a clinical treatment preference).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 84 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01714596
• Other Study ID Numbers: METRC POvIV
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Major Extremity Trauma Research Consortium
• Original Responsible Party: Same as current
• Current Study Sponsor: Major Extremity Trauma Research Consortium
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: William T Obremskey, MD; Vanderbilt University Medical Center
• Principal Investigator: Renan Castillo, PhD; Johns Hopkins Bloomberg School of Public Health
• Study Director: Tara Taylor, MPH; Johns Hopkins Bloomberg School of Public Health

• PRS Account: Major Extremity Trauma Research Consortium
• Verification Date: February 2021