PI: Dr. William Obremskey (Vanderbilt University Medical Center)

1. PI: Dr. William Obremskey (Vanderbilt University Medical Center) A Prospective Randomized Trial to Assess PO versus IV Antibiotics for the Treatment of Early Post-op Wound Infection after Extremity Fractures (POvIV Study)RESEARCH COORDINATOR TRAINING October 22, 2013

2. Background and Study Rationale • Study Aims • Study Outcomes • Inclusion/Exclusion criteria • Study Procedures • Patient Enrollment • GlowCaps • Adherence • Insurance Co-Pay Reimbursement • Data collection AGENDA

3. Prevention or control of infections remains a major goal in the care of both military and civilian casualties. The development of an infection prolongs care, increases costs and risks long term local sequelae. Infections may lead to amputation or sepsis that can result in death. • Costs of PO vs. IV Antibiotics: cost-reductions are two- to ten-fold when oral antibiotic therapy is compared to intravenous therapy the cost savings associated with oral as opposed to intravenous therapy can range from $7,476 to $15,868 per patient. • Both intravenous and oral antibiotic therapy are being used to treat post-operative wound infections, however the equivalence of oral versus intravenous therapy to treat wound infection after internal fixation of extremity fractures has not been definitively established in a randomized clinical trial. BACKGROUND

4. An informal survey of METRC investigators from 22 trauma centers conducted as part of preparation of this protocol found that 32% of respondents do not use oral antibiotics, 50% of use them for between 1 and 15 % of their patients, and 18% of respondents use oral antibiotics for more than 15% of their patients. Although it is clear that IV antibiotic therapy is the preferred or “gold standard” treatment for post-operative wound infections, our survey indicates that despite limited data on the efficacy of oral treatment for this indication, it is being used by more than two thirds of clinicians for some patients. We would like to explore outcomes of the use of PO and IV medication to determine efficacy, adherence and cost. RATIONALE

5. Objective: To investigate the efficacy of oral (per os, (PO)) antibiotic therapy versus intravenous (IV) antibiotics in the treatment of acute infection after fixation of fractures or fusion of joints. PovIV Study

6. Specific Aim 1: 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. • 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.

7. Outcome Measures: The primary study endpoint is study injury related surgical interventions by one year. Additional outcome measures include treatment failure, re-hospitalization for complication, infection, adherence and patient satisfaction with care. Outcomes

8. Primary outcome: Treatment Failures defined as: • Wound problems requiring surgery more than 2 weeks after the initial debridement or fusion surgery and randomization. • Patients that have culture positive recurrence of infection prior to bony union. Recurrence of infection will be considered to be present based on clinical suspicion of recurrence of infection with either: • Persistently elevated, or progressively increasing ESR and CRP levels in a patient with non-inflammatory arthritis • Recurrent wound drainage.

9. Among patients with plate fixation, progressive radiographic loosening of the plate, as defined by progressive development of radiolucent lines, breakage of the implant, or loss of reduction of the fracture. • Joint erosion due to infection that results in joint fusion or amputation to eradicate infection. • Patients who develop an infection with a new organism, not identified at the time of the previous infection will be considered to have a new infection. • Patients that develop adverse reactions to any of the antibiotics that causes a change from one form of administration to the other. PRIMARY OUTCOMES (TMT Failure CONTD)

10. Rehospitalization for complication defined as: • Re-admission to the hospital secondary to the treatment of the deep wound infection associated with the index closed fracture plate fixation for a defined set of complications. The list of complications includes: amputation, infection, flap failure, osteomyelitis, as previously defined (Bosse 2002). • Any complication of IV access requiring re-hospitalization including, but not limited to line sepsis, DVT in same extremity as IV access, pneumothorax or line change due to malfunction. • Admission due to antibiotic use such as renal or liver failures, hypersensitivity, or bone marrow suppression. • Amputation above the level of injury SECONDARY OUTCOMES

11. Patient Adherence • Health Care Costs • Patient Satisfaction • Amputation • Nonunion • Infection SECONDARY OUTCOMES Continued

12. See Attachment INCLUSION & EXCLUSION CRITERIA

13. CRF00 should be completed and entered into REDCap for “screening population”, defined in CRF00 as “all patient, age 18-84, with long bone fractures, and suspected to have a wound infection” Screening

14. Approximately 264 (132 per arm)will be enrolled in one of two randomized arms (PO v IV) over a 2 year period. • The study PI will be available via pager to answer any questions regarding eligibility. Please contact the MCC with all questions. • If allowed by local IRB, patients can be enrolled in POvIV and another METRC or non-METRC study PATIENT ENROLLMENT

15. Review of CRFOO TIMING OF SCREENING AND CONSENT

16. Weekly Calls (weeks 1-6) • Patients in both arms of the study • VANDY Study staff will call with adherence questions • Provide info in case of low adherence • RC –Notify Pt. of calls happening • A study staff member will be calling • Good time to reach you • Preferred phone number • 1x per week for the 6 weeks of study meds. • They will ask how you are doing and if you had any problems with the meds or med changes STUDY PROCEDURES: WEEKLY CALLS

17. The MCC will provide all sites 2 types of patient education inserts in addition to the standard POvIV study insert. These will be used to educate patients at the bedside after randomization • Adherence-Identifies the importance of taking all of the prescribed study medications • Glowcaps (PO only) – reminder for the pt. re: how to use the GlowCaps • Spanish and English Versions • Record that the pt. received the education on CRF00 PATIENT EDUCATION FOR POIV

18. During Randomization • Review Adherence insert • Review GlowCap instructions • Contact Information (pt. business card/med changes/time) • Reminder of procedures for reimbursing co-pays • GlowCaps Education (PO arm only) • 2 pieces for GlowCaps (cap and nightlight) • Explain data transmitter internally • Plug to central location (color indicators) • Taking the GlowCap with you • Reminder about adherence calls GLOWCAPS (PO ARM ONLY)

19. After Randomization (What you need to have ready…) • Sample for Demonstration • GlowCaps Insert • Adherence Education Insert • Prescriptions • Patient issued GlowCap Bottles GLOWCAPS (PO Only)

20. Some PO medications may have a substantial co-pay. • The POvIV study will reimburse participants • Use of Reimbursement log for METRC CC • Participant must present a original receipt at a study follow-up visit • RC must submit invoice to the MCC REIMBURSING INSURANCE CO-PAYS

21. PATIENT CO-PAY REIMBUSREMENT LOG

22. AE/SAE REPORTING REQUIREMENTS

23. Case Report Form Binder • Study related case report forms • Serious Adverse Event form • Final Status form • Administrative Forms (on REDCap) • Missed/Incomplete/Out of Window Visit • Patient Search • Patient Transfer • Protocol Deviation • Unanticipated Event • Contact Log DATA COLLECTION

24. CRF Binders • Patient Enrollment Materials (English & Spanish) Study Brochures Adherence Insert PO GlowCaps Insert Clinician Screening Cards/Participant Business Cards • GlowCaps A shipment of paired GlowCaps will be sent to every site initially; Caps will be restocked as needed. Please communicate with Tara for supplies. STUDY MATERIALS

25. For questions about eligibility: Bill Obremskey(PI)- pager # included in the protocol • For technical (REDCap) assistance: metrc@tech.org • For questions related to all other study procedures: • Post questions to METRC Bulletin Board • If you have questions specific to your site, contact Tara Taylor tjtaylor@jhsph.edu STUDY CONTACTS

26. Next Trainings: • Review of Pertinent CRF information • Glow Caps Overview • Medication Adherence Overview • Binders, Screening Cards etc. 

27. Thank you!