Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02099240
Other study ID # 14.0185
Secondary ID
Status Terminated
Phase Early Phase 1
First received
Last updated
Start date March 6, 2014
Est. completion date November 7, 2018

Study information

Verified date April 2021
Source University of Louisville
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Based on the current literature, investigators hypothesize that patients with osteomyelitis who are treated with the standard approach of intravenous antibiotics for the full duration of therapy will have the same clinical outcomes as patients treated with the experimental approach of intravenous antibiotics with early switch to oral antibiotics. The primary objective of this study is to compare patients with osteomyelitis treated with the standard approach of intravenous antibiotics for the full duration of therapy versus patients treated with intravenous antibiotics with an early switch to oral antibiotics in relation to clinical outcomes at 12 months after discontinuation of antibiotic therapy. Secondary objectives of the study include the evaluation of adverse events related to the use of antibiotics as well as the cost of care evaluated from the hospital perspective.


Description:

1.1. Background Information Osteomyelitis is a common disease associated with significant morbidity and high cost (1). The treatment of osteomyelitis can be challenging requiring prolonged administration of antibiotics and extensive surgical procedures. Even when the infection is treated, the relapse rate is as high as 20% (2). When a bone is infected, the local multiplication of bacteria produces a local inflammatory response with presence of neutrophils and macrophages with areas of microthrombi and avascular necrosis. If a significant area of avascular necrosis develops, a segment of the bone without any blood supply can become separated and form a sequestrum. Since infection of sequestrum occurs in most patients with osteomyelitis, it is considered that in addition to antibiotic treatment, the patient requires surgical intervention for removal of necrotic bone. 1.2. Scientific Rationale There is agreement regarding the minimal duration of antibiotic therapy for patients with osteomyelitis. Since an infected bone may take 3 to 4 weeks to re--- vascularize, the duration of therapy should be a minimum of 4 to 6 weeks of antibiotics. Because different organisms can cause osteomyelitis, the initial antibiotic therapy during hospitalization should include broad---spectrum antibiotics to cover the most likely organisms. As part of the initial management, a bone biopsy is regularly performed to identify the particular etiologic agent. Once the organism and its antimicrobial susceptibilities are known, the spectrum of antibiotic therapy is narrowed, and the antimicrobial therapy continues with an antibiotic that is targeted according to the susceptibility of the identified pathogen. Targeted antibiotic therapy in patients with osteomyelitis is usually performed after 3 to 5 days of broad spectrum antibiotics, since this is the time required by the microbiology department to generate antimicrobial susceptibilities after the bone biopsy is performed. In regard to the route of antibiotic administration, the standard approach is to use an intravenous antibiotic. 1.3. Potential Risks A potential risk for the use of an early switch to oral antibiotics in patients with osteomyelitis is that the blood level achieved with oral antibiotics may not be high enough to attain clinical resolution of the infection. 1.4. Potential Benefits There are several potential benefits of using oral antibiotics instead of intravenous antibiotics. First, avoiding a peripherally inserted central line eliminates the risk of line infection and line---associated deep vein thrombosis. An early switch to oral antibiotics may also facilitate early hospital discharge. A shorter hospital stay will decrease the risk of hospital---associated complications such as hospital---acquired infections. Further, the patients' quality of life may be better without a central line. Finally, the total cost of therapy will be significantly reduced with oral therapy. 2. Methods 2.1. Trial design & setting This will be a prospective, randomized, unblinded clinical trial to define if the clinical outcomes of patients with osteomyelitis treated with the experimental approach of intravenous antibiotics with an early switch to oral therapy is non---inferior to the current standard approach of intravenous antibiotics for the full duration of therapy. 2.8. Sample Size & Statistical Analysis The null hypothesis for this study will be as follows: H0: πs --- πe ≤ ---Δ Where πs is the proportion of clinical failures in the intravenous therapy only group, πe is the proportion of clinical failures in the intravenous therapy plus early switch to oral therapy group, and Δ is the non---inferiority margin. The alternative hypothesis will be: HA: πs --- πe > ---Δ We expect that there will be a 20% clinical failure rate for the primary outcome in both the intravenous antibiotic therapy group and the intravenous antibiotic therapy plus early switch to oral antibiotic therapy group. The study will be powered at 80% with Δ of 0.1. A total of 396 patients will be needed to obtain a 95% confidence interval for the difference in failure rates between the two groups that has a lower limit above ---Δ. If the lower limit of this 95% confidence interval for the 10 difference in clinical failure rates between the two arms is above -Δ, non---inferiority will be met. Considering that approximately 15% of patients will be lost during study follow---up, a total of 456 patients will be enroll in the trial to obtain the 396 patients necessary for final analyses. 3. Data Quality Management Plan 3.1. Overview of the Clinical and Translational Research Support Center The University of Louisville Clinical and Translational Research Support Center (CTRSC) will be responsible for data collection, data quality, and data analysis for this project. The CTRSC (http://www.ctrsc.net) is a multi---disciplinary team comprised of professionals in medicine, public health, statistics, and computer science. The team has considerable experience managing and supporting single---site and multi---center clinical research studies. Specifically, members of the CTRSC will be responsible for: - Study design - Development of data collection forms - Development of study manual 11 - Development of electronic Internet base data entry system - Providing instruction on use of forms and data entry system - Development of study database - Tracking subject enrollment - Overseeing data transmission - Providing data management - Handling data validation - Protecting confidentiality of data - Performing feasibility evaluation The data quality team leader for this project will be Dr. Robert Kelley with assistance from Dr. Timothy Wiemken and Dr. Paula Peyrani. The CTRSC has access to the University of Louisville's high---performance computing cluster, which consists of 312 IBM iDatplex nodes each with two Intel Xeon quad--- core processors for 2496 total cores. The cluster is equipped with a variety of statistical and bioinformatics software including SAS, R, Matlab, ClustalW, and Blast, and C, Fortran, Perl, and Python libraries. In addition, the CTRSC has several iMac and IBM---compatible workstations with several data management and analysis packages installed including R, Matlab, SQL Server 2012, SAS, SPSS, Eclipse, Visual Studio .NET 2010, MySQL Server 5.1, Tableau 8.0, and REDCap. 3.2. Purpose of Data Quality Management Plan The purpose of this data quality management plan is outline the procedures and processes necessary to: 1. Ensure the data collection and data management for the study are conducted in a manner consistent with University of Louisville standards as well as state and federal regulations. 2. Ensure that data collected are accurate and complete when verified against source documents. 3. Provide approaches for early interception and correction of errors in data collection. 4. Identify areas where specific education and training efforts regarding data collection need to be focused. 5. Outline the tools that will be used to monitor and assess data quality. 6. Outline the Data Quality Management Team meeting schedule for this project. 3.3. Data Capture Primary data collection will be performed by a qualified study coordinator(s) who will abstract subject data from the electronic medical record onto a paper case report form. Once the paper case report form is complete, the study coordinator or other designee will enter the data into a secure, web---based clinical data management system.


Recruitment information / eligibility

Status Terminated
Enrollment 11
Est. completion date November 7, 2018
Est. primary completion date November 7, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility Inclusion Criteria: - Only adult patients will be invited to participate in this trial (age = 18 years). A patient will be considered a candidate to participate in this trial if the following two inclusion criteria are present: 1. Isolation of an organism from bone culture that is susceptible to intravenous and oral antibiotics. 2. Plus at least one of the following: - Evidence of local inflammatory response, manifested as local pain, edema, erythema, warmth, or drainage. - Evidence of systemic inflammatory response, manifested as fever, elevated C---reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), or white blood cell count. - *Osteomyelitis---compatible findings on plain radiograph, computed tomography, bone scan, magnetic resonance imaging, or positron emission tomography. - Pathology report indicative of osteomyelitis. Exclusion Criteria: - A patient will not be considered as a candidate to participate in this study if the study team expects the subject to be non---compliant with the study follow---up clinic visit.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
oral antibiotics
intravenous antibiotics with early switch to oral antibiotics, antibiotic type will be dependent on bacteria type
Procedure:
intravenous antibiotics
intravenous antibiotics for the full duration of therapy, antibiotic type will be dependent on bacteria type

Locations

Country Name City State
United States University of Louisville Louisville Kentucky

Sponsors (2)

Lead Sponsor Collaborator
Julio Ramirez University of Louisville

Country where clinical trial is conducted

United States, 

References & Publications (6)

Conterno LO, da Silva Filho CR. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD004439. doi: 10.1002/14651858.CD004439.pub2. Review. Update in: Cochrane Database Syst Rev. 2013;9:CD004439. — View Citation

Haas DW, McAndrew MP. Bacterial osteomyelitis in adults: evolving considerations in diagnosis and treatment. Am J Med. 1996 Nov;101(5):550-61. Review. — View Citation

Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis. 2005 May;9(3):127-38. Review. — View Citation

Lew DP, Waldvogel FA. Osteomyelitis. Lancet. 2004 Jul 24-30;364(9431):369-79. Review. — View Citation

Peyrani P, Allen M, Seligson D, Roberts C, Chen A, Haque N, Zervos M, Wiemken T, Harting J, Christensen D, Ramirez R. Clinical outcomes of osteomyelitis patients infected with methicillin-resistant Staphylococcus aureus USA-300 strains. Am J Orthop (Belle — View Citation

Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med. 1970 Jan 22;282(4):198-206. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Clinical Failures Clinical failure will be defined as clinical or laboratory evidence of infection collected from the patient's medical record documents. 1 month
Secondary Evaluation of adverse events related to the use of antibiotics Antibiotic---related adverse events will be defined according to the Food and Drug Administration adverse events listed in the package insert of the antibiotic prescribed for each subject. 1 month
Secondary Cost of care from the hospital perspective Costs will be calculated from the hospital perspective and will include the costs of the antibiotic therapy, home healthcare (nursing--- and infusion---related), and length of hospital stay. 12 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04563325 - Oral-only Antibiotics for Bone and Joint Infections in Children Phase 4
Not yet recruiting NCT06402292 - Surgical Treatment of Osteoarticular Infections Using Bioactive Bone Substitute N/A
Completed NCT03846804 - Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections N/A
Active, not recruiting NCT04945434 - Clinical Effectiveness of S53P4 Bioactive Glass in Treatment of Long-bone Chronic Osteomyelitis N/A
Recruiting NCT06084754 - Effect of Pulsed Electromagnetic Field Stimulation on Localized Pediatric Osteomyelitis N/A
Recruiting NCT05177107 - Bacteriophage Therapy in Patients With Diabetic Foot Osteomyelitis Phase 2
Recruiting NCT04554108 - Acute Non-severe Osteomyelitis in Children - Outpatient Management Strategy With Oral Antibiotic Therapy Compared to a Standard Strategy With Conventional Hospitalization and Intravenous Antibiotic Therapy: a Randomized Open-label Non-inferiority Study With Bayesian and Medical-economic Analyses. N/A
Recruiting NCT02128256 - CERAMENT™|G - Bone Healing and Re-infection Prophylaxis Phase 4
Terminated NCT01612962 - Diagnostic Tests to Help Determine Osteomyelitis N/A
Terminated NCT03091439 - Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Patients With Osteomyelitis Phase 2
Recruiting NCT04936958 - RETR(Osteomyelitis)
Completed NCT03802552 - Cefadroxil and Cephalexin Drug Levels and Dosing in Pediatric Musculoskeletal Infections Phase 1
Completed NCT03559530 - Acinetobacter Baumannii-related Osteomyelitis: Clinical and Epidemiological Characterization
Completed NCT00324922 - Vancomycin Or Trimethoprim/Sulfamethoxazole for Methicillin-resistant Staphylococcus Aureus Osteomyelitis Phase 3
Completed NCT02084147 - PET-MRI in Diagnosing Patients With Cancer, Cardiac Diseases, or Neurologic Diseases N/A
Withdrawn NCT02344511 - Dalbavancin vs Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis Phase 3
Completed NCT00402064 - The Influence of Bisphosphonates in the Oral Cavity in Children N/A
Terminated NCT02168816 - Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for Osteomyelitis Phase 2
Completed NCT02685033 - Study on the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Participants With Osteomyelitis Phase 2
Completed NCT02335905 - Ceftaroline for Treatment of Hematogenously Acquired Staphylococcus Aureus Osteomyelitis in Children Phase 1/Phase 2