Oral vs IV Antibiotics for Infected Broken Bones

(POvIV2 Trial)

Recruiting at 10 trial locations

Overseen By William Obremskey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Major Extremity Trauma Research Consortium

Must be taking: Antibiotics

Disqualifiers: Amputation risk, Investigational therapy, Incarceration, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether oral (PO) antibiotics are as effective as intravenous (IV) antibiotics for treating infections in improperly healed broken bones. It examines if taking pills can match the effectiveness of medicine delivered through a vein when combined with surgery. The trial will assess factors such as the need for additional surgeries, any complications, and hospital stays. It seeks participants who have undergone surgery to fix a broken bone that didn't heal properly and now have an infection. Those dealing with an infected broken bone after surgery may find this trial suitable. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both oral (taken by mouth) and intravenous (given through a vein) antibiotics are generally safe for treating bone and joint infections. Studies have found that oral antibiotics can be just as effective as IV antibiotics in many situations. In fact, research suggests that both methods are equally safe for most people.

The failure rate, which measures how often the treatment doesn't work as expected, is low for both types of antibiotics. One study found that about 13% of patients who switched to oral antibiotics experienced treatment failure, indicating that most patients tolerate oral antibiotics well.

For IV antibiotics, the safety data is also encouraging. There are no major differences in safety compared to oral antibiotics, although some studies noted a slightly higher chance of the infection returning with oral antibiotics.

Both treatments have been used safely in many patients, and there is no strong evidence of major safety concerns with either option. For those considering joining a trial, these findings suggest that both types of antibiotics are safe choices. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about comparing oral (PO) and intravenous (IV) antibiotics for treating infected broken bones because these two methods offer different benefits. Oral antibiotics are easy to take and can be managed at home, which is convenient for patients and could reduce hospital stays. On the other hand, IV antibiotics are often considered more potent, especially for severe infections, as they are delivered directly into the bloodstream. This trial aims to determine if oral antibiotics can be as effective as IV antibiotics, potentially simplifying treatment and improving patients' quality of life while still ensuring effective infection management.

What evidence suggests that this trial's treatments could be effective for infected broken bones?

This trial will compare the effectiveness of oral antibiotics and intravenous (IV) antibiotics for treating infected broken bones. Research has shown that oral antibiotics work as well as IV antibiotics for bone and joint infections. Specifically, studies found that patients taking oral antibiotics healed and controlled their infections as effectively as those receiving IV antibiotics. Those on oral antibiotics experienced fewer complications, and the treatment often cost less. Both methods successfully prevented additional surgeries and recurrence of infections. Overall, oral antibiotics offer a practical option that matches the effectiveness of IV antibiotics. ^{2 6 7 8 9}

Who Is on the Research Team?

William Obremskey, MD

Principal Investigator

Vanderbilt Medical Center

Renan Castillo, PhD

Principal Investigator

Johns Hopkins Bloomberg School of Public Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with infected nonunion fractures after internal fixation, which haven't healed properly despite previous surgery. Participants must need at least 6 weeks of antibiotics and meet specific infection criteria. Those not fitting this description or having other conditions that could interfere with the study are excluded.

Inclusion Criteria

My broken bone hasn't healed properly after surgery and it's been over 3 months.

I have an infection confirmed by a doctor and am on antibiotics for 6+ weeks.

Exclusion Criteria

Patients with a high risk of amputation based on the initial managing physician

Incarcerated or institutionalized patients

Patients with a prior history of chronic infection at the index site before fracture fixation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral (PO) or intravenous (IV) antibiotics for 6 weeks post hospitalization for infected nonunion

6 weeks

Visits at 2 weeks and 6 weeks for laboratory evaluation and clinical follow-up

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for re-hospitalization, treatment failure, infection, nonunion, and amputation

12 months

Follow-up visits at 3 months, 6 months, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• IV antibiotics
• PO antibiotics

Trial Overview The trial compares oral (PO) versus intravenous (IV) antibiotics in treating infected nonunion fractures after surgical bone repair. It aims to determine if taking pills is as effective as IV treatment when combined with proper surgery. Outcomes include re-admission rates, treatment failure, complications within a year, and overall costs.

How Is the Trial Designed?

Group I: Standard of Care Intravenous (IV) antibiotics Active Control 1 Intervention

An intervention in this study includes randomization of patients with an infected nonunion to intravenous (IV) antibiotics for up to 6 weeks post hospitalization. No medications will be provided by the study. Study participants will be prescribed their IV antibiotics by their treating physician and the specific type will depend on their infection diagnosis. Medications will be obtained using health insurance and/or resources available at the treating facility therefore the mode of antibiotics utilized as standard of care will vary across participating sites. Sites will follow their standard of care delivery for antibiotics and the study will defer to this standard.

Group II: Standard of Care PO (oral) antibiotics Active Control 1 Intervention

An intervention in this study includes randomization of patients with an infected nonunion to standard of care PO (oral) antibiotics for up to 6 weeks post hospitalization. No medications will be provided by the study. Study participants will be prescribed their oral antibiotics by their treating physician and the specific type will depend on their infection diagnosis. Medications will be obtained using health insurance and/or resources available at the treating facility therefore the mode of antibiotics utilized as standard of care will vary across participating sites. Sites will follow their standard of care delivery for antibiotics and the study will defer to this standard.

Who Is Running the Clinical Trial?

Major Extremity Trauma Research Consortium

Lead Sponsor

Trials

32

Recruited

27,400+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a study of 95 children treated for acute osteomyelitis, the university hospital had a higher rate of intravenous antibiotic use at discharge (95%) compared to the county hospital (65%), indicating a potential difference in treatment practices.

Despite the higher use of intravenous antibiotics at the university hospital, the recurrence and complication rates were not significantly different from the county hospital, suggesting that oral antibiotics may be a viable alternative and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous versus oral outpatient antibiotic therapy for pediatric acute osteomyelitis. Liu, RW., Abaza, H., Mehta, P., et al.[2021]

In a study of 328 patients with bone and joint infections, implementing the OVIVA trial findings allowed 66.1% of patients to switch to effective oral antibiotics, demonstrating that oral therapy is a viable alternative to intravenous treatment in real-world settings.

Postimplementation, patients experienced a 4-day reduction in hospital stay and a significant cost savings of £2764.28 per patient, while the rate of adverse drug reactions requiring treatment changes increased from 21.0% to 37.1%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Experience of Implementing Oral Versus Intravenous Antibiotics (OVIVA) in a Specialist Orthopedic Hospital. Azamgarhi, T., Shah, A., Warren, S.[2021]

Current guidelines recommend 4-6 weeks of IV antibiotics for infective endocarditis (IE), but recent evidence suggests that oral antibiotics can achieve safe and effective serum levels, challenging the need for prolonged IV therapy.

The largest randomized controlled trial, the POET trial, found that oral therapy is non-inferior to prolonged IV therapy in stable patients with left-sided IE, supporting a potential shift towards oral antibiotics as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antibiotics for infective endocarditis: a clinical review. Brown, E., Gould, FK.[2021]

A quality improvement initiative at a large children's hospital successfully increased the discharge rate of patients with acute osteomyelitis on oral antibiotics from virtually 0% to a maximum of 9 cases, achieving a goal of at least 70%.

The intervention demonstrated that treatment failures and complications remained low, with no significant differences in hospital length of stay or charges, indicating that oral antibiotics are a safe and effective alternative to intravenous therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antibiotics at discharge for children with acute osteomyelitis: a rapid cycle improvement project. Brady, PW., Brinkman, WB., Simmons, JM., et al.[2021]

A systematic review of 10 studies found no significant difference in the overall rate of adverse events between oral and intravenous antimicrobial therapies, suggesting that both routes are similarly safe.

Injection site reactions were more common with intravenous therapy, but no serious drug-related adverse events were reported, indicating that both methods are generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials. Kouranos, VD., Karageorgopoulos, DE., Peppas, G., et al.[2018]

A systematic review of five studies involving 580 patients found that sequential IV/PO antibiotic therapy does not increase the risk of complications compared to continuous IV antibiotics, indicating it is a safe alternative.

The study shows that using sequential IV/PO antibiotics is noninferior to IV-only therapy in preventing postoperative abscesses, wound infections, and readmissions, suggesting it could be a cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous versus intravenous/oral antibiotics for perforated appendicitis in pediatric patients: a systematic review and meta-analysis. Wang, C., Li, Y., Ji, Y.[2020]

In a study of 1054 adults with complex orthopedic infections, oral antibiotic therapy was found to be noninferior to intravenous therapy, with a treatment failure rate of 13.2% for oral antibiotics compared to 14.6% for intravenous antibiotics, indicating similar effectiveness.

The incidence of serious adverse events was comparable between the two groups, but catheter complications were significantly more common in the intravenous group (9.4% vs. 1.0%), suggesting that oral antibiotics may offer a safer alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral versus Intravenous Antibiotics for Bone and Joint Infection. Li, HK., Rombach, I., Zambellas, R., et al.[2022]

A study involving 1054 adults with bone and joint infections found that oral antibiotics are just as effective as intravenous antibiotics for the first 6 weeks of treatment, with a treatment failure rate of 14.62% for IV therapy compared to 13.16% for oral therapy, meeting the non-inferiority criterion.

Oral therapy was associated with fewer complications, particularly fewer IV catheter-related issues, and was more cost-effective, saving approximately £2740 per patient without compromising quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT. Scarborough, M., Li, HK., Rombach, I., et al.[2021]

In a study of 58 children with febrile neutropenia, there was no significant difference in treatment outcomes between oral antibiotic therapy (ciprofloxacin and amoxicillin-clavulanate) and intravenous therapy (cefepime), with treatment failure rates of 51.2% and 45.8%, respectively.

Both treatment groups had similar lengths of hospital stays, averaging around 7 to 8 days, indicating that oral therapy may not be less effective than intravenous therapy, but further research is needed to establish oral therapy as a standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral vs. intravenous empirical antimicrobial therapy in febrile neutropenic patients receiving childhood cancer chemotherapy. Cagol, AR., Castro Junior, CG., Martins, MC., et al.[2020]

A set of 16 measurable conditions for safely switching from intravenous to oral antibiotics in hospitalized adults was developed through a rigorous expert panel process, ensuring clinical relevance and safety.

Key criteria include stable blood pressure, absence of severe infections or gastrointestinal issues, and the ability to achieve adequate drug concentrations orally, which can enhance clinical decision-making and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of operationalized intravenous to oral antibiotic switch criteria. Akhloufi, H., Hulscher, M., Melles, DC., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39841468/

Oral vs Intravenous Antibiotics for Fracture-Related Infections Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S8756328225001061

Oral versus intravenous antibiotics for bone and joint ... Appropriately selected PO antibiotic regimens demonstrate comparable efficacy and safety to IV therapy in bone and joint infections.

3. cidrap.umn.edu cidrap.umn.edu/antimicrobial-stewardship/mixed-results-trial-comparing-oral-iv-antibiotics-fracture-related

Mixed results in trial comparing oral, IV antibiotics for ... Patients receiving oral versus intravenous (IV) antibiotics for fracture-related infections (FRIs) had similar reoperation and reinfection rates.

4. aaos.org aaos.org/aaosnow/2025/june/clinical/clinical06/

A Look at the Evidence: Should Orthopaedic Surgeons ... The authors concluded that oral antibiotic therapy is noninferior to IV therapy when used during the first 6 weeks of treatment for bone or ...

5. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/list/print/NCT05699174

PO vs IV Antibiotics for the Treatment of Infected Nonunion ... An intervention in this study includes randomization of patients with an infected nonunion to intravenous (IV) antibiotics for up to 6 weeks ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12424555/

Implementation of oral versus intravenous antibiotics in ... We found a comparably low failure rate of 13% among patients who were able to transition to oral antibiotics when applying the treatment ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01714596

Randomized Trial to Assess PO Versus IV Antibiotics (POvIV) 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: ...

8. paleyinstitute.org paleyinstitute.org/wp-content/uploads/2025/03/38-A-Prospective-Randomized-Trial-to-Assess-Oral-Versus-Intravenous-Antibiotics-for-the-Treatment-of-Postoperative-Wound-Infection-After-Extremity-Fractures-POvIV-Study.pdf

A Prospective Randomized Trial to Assess Oral Versus ... The main aim of the POvIV study is to evaluate the effect of treatment of postoperative wound infection in bones after fracture fixation or joint fusion with.

9. academic.oup.com academic.oup.com/ofid/article/11/12/ofae683/7902026

Implementing Oral Antibiotics for Bone and Joint Infections All data were recorded in REDCap. Within the postguideline cohort, we also examined primary and secondary outcomes among patients discharged on IV antibiotics ...