The Safety of Hemophilia Product Use: a Simulation Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5914-5914
Author(s):  
Stephanie Chiuve ◽  
Daniel Gallo ◽  
Christopher Rowan ◽  
Leonard A. Valentino
Keyword(s):  
Treatment Group ◽  
Safety Concern ◽  
Standard Of Care ◽  
Current Therapy ◽  
Published Data ◽  
Sample Sizes ◽  
Investigational Agent ◽  
Fold Reduction ◽  
Current Therapies ◽  
Bleeding Episodes

Abstract Background:In hemophilia patients with inhibitors, the primary safety concern associated with the administration of bypassing agents, such arecombinant factor VIIa (rFVIIa)andFactor Eight Inhibitor Bypass Activity (FEIBA)to manage bleeding episodes is the risk ofthromboembolic events (TEs). Replacement FVIII may also increase TEs in patients with hemophilia without inhibitors, although the incidence of TE is extremely rare. The low incidence of hemophilia and low rate of TE associated with current therapies in these patients provide a significant challenge to study the comparative safety of novel non-factor therapies with the current standard of care. Aims: We aimed to estimate the sample size needed to adequately power a clinical trial that would detect a reduction in TEs in hemophilia patients exposed to a hypothetical investigational agent compared to current therapies for the management of bleeding episodes (FVIII replacement, FEIBA and rFVIIa). Methods: We conducted a simulated power analysis to quantify the number of infusions that would be needed in each treatment arm (investigational therapy vs. current therapy) to detect a reduction in the rate of TE in hemophilia patients across a range of effects. Based on published data, the rate of TE was 2 per 106 infusions of replacement FVIII. We assumed conservative rates of TE of 2 per 105 infusions of replacement FVIII to account for the potential imprecise rates estimated from the low number of events observed in prior studies. In the MedWatch database, the rate of TE was 8.24 per 105 infusions of FEIBA and 24.6 per 105 infusions of NOVOSEVEN. To account for the known underreporting of adverse events in this database, we assumed conservative estimates of and, 1.34 per 103 infusions of FEIBA and 3.12 per 103 infusions of NOVOSEVEN. We applied a two-sided Z test with pooled variance and targeted the significance level of the test at 0.05 and the power at 0.8. Results: The number of infusions needed to detect a significant reduction TE rate in patients exposed to the investigational agent compared to all 3 standard of care therapies across a range of potential effects are provided in the Table. Sample sizes of 735,821 infusions per treatment group (replacement FVIII vs. investigational agent) are needed to achieve 80% power to detect a 5 fold reduction in the rate of TE among hemophilia patients exposed to the investigational agent compared to replacement FVIII. Over 1 million infusions per treatment group would be needed to detect a 2 fold reduction in rate of TE comparing an investigational agent to replacement FVIII. Sample sizes of 35,108 infusions in each treatment group would be required to detect a 2-fold decrease in TE rates in patients exposed to the investigational agent compared to FEIBA. To detect a 2 fold reduction in rate of TE in patients receiving the investigational agent compared to rFVIIa, the study would require 15,058 infusions in each treatment group. Conclusions: Current therapies to manage bleeding episodes in patients with hemophilia have demonstrated a high degree of safety.Clinical trials of alternative non-factor therapies with mechanisms of action that differ from the standard of care will require extremely large samples sizes and/or large reduction in TE risk to demonstrate significantly greater safety with respect to TE. Disclosures Chiuve: Shire: Employment. Gallo:Shire: Employment. Rowan:Baxalta: Consultancy. Valentino:Shire: Employment.

scholarly journals Assessing Protection from Intracranial Hemorrhage in Clinical Studies for Investigational Agents in Patients with Hemophilia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5915-5915
Author(s):  
Daniel Gallo ◽  
Stephanie Chiuve ◽  
Christopher Rowan ◽  
Leonard A. Valentino
Keyword(s):  
Clinical Studies ◽  
Standard Of Care ◽  
Severe Hemophilia ◽  
Current Standard ◽  
Investigational Agent ◽  
Investigational Treatment ◽  
Fold Reduction ◽  
Investigational Agents ◽  
Replacement Factor

Abstract Background: Intracranial hemorrhage (ICH) is a serious complication for patients with Hemophilia. In the Universal Data Collection (UDC) program (Witmer C et al., 2011), the rate of ICH in patients with hemophilia (PWH) was 3.9 per 1000 patient-years, with the majority of events (74.4%) taking place in patients with severe hemophilia. The incidence of mortality for hemophilia patients experiencing ICH approaches 20%. Prophylaxis with replacement factor remains the standard of care for PWH and is efficacious in reducing the incidence of ICH by 48% in HIV-negative, severe hemophilia patients and by 50% in severe hemophilia patients with inhibitors. Multiple investigational non-factor products are currently undergoing clinical evaluation for the treatment of Hemophilia. Given their different mechanisms of action, it is unknown if they will provide the same level of protection from ICH as the current standard of care. Aims: We aimed to estimate the sample size needed to power a clinical study adequately to detect a reduction in the risk of ICH in PWH using a hypothetical investigational agent compared to the rates of ICH observed in the UDC Hemophilia cohort. Methods: We conducted a simulated power analysis to quantify the number of patients needed to detect a reduction in risk of ICH in PWH exposed to a hypothetical investigational agent compared to the risk of ICH observed in the UDC cohort. Based on published data, we assumed an overall ICH risk of 1.9% over a 10-year follow-up (average follow-up 5 years). We assumed a risk of ICH of 1.7% over an average of 5 years in patients prescribed prophylaxis with replacement factor and a risk of mortality due to ICH within patients with hemophilia of 0.4%. We used a two-sided Z test with pooled variance and targeted the significance level of the test at 0.05 and the power at 0.8. Results: A sample size of 11,595 patients per group followed for 1 year is required to achieve 80% power to detect a 2-fold reduction in ICH risk for patients receiving investigational treatment compared to the overall observed risk in PWH receiving treatment at federally funded HTCs. Sample sizes of 13,650 would be required per group, to demonstrate a 2-fold reduction in ICH risk for patients receiving investigational treatment vs. patients prescribed prophylaxis with replacement factor. Additionally, sample sizes of 11,737 per group, would be required to achieve 80% power to detect a 2-fold reduction in the risk of ICH mortality in a population of patients treated with an investigational agent vs. patients with hemophilia under the current standard of care. Conclusions: The relatively high mortality associated with incidence of ICH, highlights a need to determine how efficacious investigational agents are in protecting from these events. However, the relatively infrequent incidence of ICH represents an obstacle for current clinical studies to adequately evaluate protection against these types of events. These analyses demonstrate that clinical trials of investigational non-factor products would require extremely large samples sizes in order to demonstrate a level of protection that is comparable or superior to that observed with the current standard of care. Additional clinical and scientific strategies will be required in order to thoroughly assess the efficacy of non-factor agents in protecting from ICH. Disclosures Gallo: Shire: Employment. Chiuve:Shire: Employment. Rowan:Baxalta: Consultancy. Valentino:Shire: Employment.

A systematic review and meta-analysis on endovascular treatment as an attractive alternative for acute superior mesenteric venous thrombosis

Vascular ◽  
2021 ◽  
pp. 170853812199127
Author(s):  
Lixin Wang ◽  
Enci Wang ◽  
Fei Liu ◽  
Wei Zhang ◽  
Xiaolong Shu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Group ◽  
Conservative Treatment ◽  
Venous Thrombosis ◽  
Endovascular Treatment ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Published Data ◽  
Mesenteric Venous Thrombosis ◽  
Surgery Group

Objective This systematic review and meta-analysis evaluated the published data on the efficacy and safety of therapies for superior mesenteric venous thrombosis (SMVT), aiming to provide a reference and set of recommendations for clinical treatment. Methods Relevant databases were searched for studies published from 2000 to June 2020 on SMVT treated with conservative treatment, surgical treatment, or endovascular approach. Different treatment types were grouped for analysis and comparison, and odds ratios with corresponding 95% confidence intervals were calculated. The outcomes were pooled using meta-analytic methods and presented by forest plots. Results Eighteen articles, including eight on SMVT patients treated with endovascular therapies, were enrolled. The treatment effectiveness was compared between different groups according to the change of symptoms, the occurrence of complications, and mortality as well. The conservative treatment group had better efficacy compared to the surgery group (89.0% vs. 78.6%, P <0.05), and the one-year survival rate was also higher (94.4% vs. 80.0%, P >0.05), but without statistical significance. As for endovascular treatment, the effectiveness was significantly higher than the surgery group (94.8% vs. 75.2%, P <0.05), and the conservative treatment group as well (93.3% vs. 86.3%, P >0.05), which still requires further research for the lack of statistical significance. Conclusions Present findings indicate that anticoagulation, as conservative treatment should be the preferred clinical option in the clinic for SMVT, due to its better curative effect compared to other treatment options, including lower mortality, fewer complications, and better prognosis. Moreover, endovascular treatment is a feasible and promising approach that is worth in-depth research, for it is less invasive than surgery and has relatively better effectiveness, thus can provide an alternative option for SMVT treatment and may be considered as a reliable method in clinical.

scholarly journals Complete metabolic response in patients with advanced nonsmall cell lung cancer with prolonged response to immune checkpoint inhibitor therapy

2021 ◽  
Vol 9 (3) ◽  
pp. e002262
Author(s):  
Justin Ferdinandus ◽  
Martin Metzenmacher ◽  
Lukas Kessler ◽  
Lale Umutlu ◽  
Clemens Aigner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Metabolic Response ◽  
Standard Of Care ◽  
Nonsmall Cell Lung Cancer ◽  
Published Data ◽  
Complete Metabolic Response ◽  
Positron Emission ◽  
Checkpoint Inhibitor Therapy

IntroductionImmunotherapy is the new standard of care in advanced nonsmall cell lung cancer (NSCLC). Recently published data show that treatment discontinuation after 12 months of nivolumab treatment is associated with shorter survival. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcomes is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients who have not progressed after 24 months of immunotherapy.MethodsThis is a retrospective analysis of 45 patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose imaging for assessment of residual metabolic activity after at least 24 months. CMR was defined as uptake in tumor lesions below background levels, using mediastinum as a reference. ResultsOut of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first-line patients. Patients with CMR were younger (median 65.7 vs 75.5, p=0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however, median follow-up was only 5.6 (range 0.8–17.0) months.ConclusionAfter a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.

Cancer-induced bone pain

2015 ◽  
Author(s):  
Lesley A. Colvin ◽  
Marie Fallon
Keyword(s):  
Bone Pain ◽  
Clinical Presentation ◽  
Clinical Problem ◽  
Current Therapy ◽  
Pain Mechanisms ◽  
Pain Syndromes ◽  
Current Therapies ◽  
Underlying Mechanisms ◽  
Laboratory Models ◽  
Major Clinical Problem

Bone is the third most common site of metastatic disease, after liver and lung, with approximately 75% of these patients suffering from related pain. Cancer-induced bone pain (CIBP) is a major clinical problem, with limited options for predictable, rapid, and effective treatment for some of the elements without unacceptable adverse effects. Our understanding of how current therapy acts is based mainly on studies in non-cancer pain syndromes, which are likely to be quite different, not only in clinical presentation, but also in terms of pathophysiology. It can be difficult to study the specific neurobiological changes associated with CIBP, although development of laboratory models of isolated bone metastases has allowed more specific study of pain mechanisms in this syndrome. In order to evaluate our current therapies properly and direct the development of new therapies logically, it is important to understand the underlying mechanisms of CIBP. This chapter discusses pain processing and the mechanisms and management of CIBP.

scholarly journals A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Timothy Devos ◽  
Tatjana Geukens ◽  
Alexander Schauwvlieghe ◽  
Kevin K. Ariën ◽  
Cyril Barbezange ◽  
...  
Keyword(s):  
Treatment Group ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Active Treatment ◽  
Standard Of Care ◽  
Active Treatment Group ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase

Abstract Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered.

scholarly journals Implementing complete mesocolic excision for colon cancer – mission completed?

2018 ◽  
Vol 3 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Roland S. Croner ◽  
Henry Ptok ◽  
Susanne Merkel ◽  
Werner Hohenberger
Keyword(s):  
Colon Cancer ◽  
Minimally Invasive Surgery ◽  
Minimally Invasive ◽  
Invasive Surgery ◽  
Complete Mesocolic Excision ◽  
Oncological Outcome ◽  
Standard Of Care ◽  
Published Data ◽  
Mesocolic Excision ◽  
Related Survival

AbstractThe definition of complete mesocolic excision (CME) for colon carcinomas revolutionized the way of colon surgery. This technique conquered the world starting from Erlangen. Nevertheless, currently new developments especially in minimally invasive surgery challenge CME to become settled as a standard of care. To understand the evolution of CME, anatomical details occurring during embryogenesis and their variations have to be considered. This knowledge is indispensable to transfer CME from an open to a minimally invasive setting. Conventional surgery for colon cancer (non-CME) has a morbidity of 12.1–28.5% and a 3.7% mortality risk vs. 12–36.4% morbidity and 2.1–3% mortality for open CME. The morbidity of laparoscopic CME is between 4 and 31% with a mortality of 0.5–0.9%. In robotic assisted surgery, morbidity between 10 and 25% with a mortality of 1% was published. The cancer-related survival after 3 and 5 years for open CME is respectively 91.3–95% and 90% vs. 87% and 74% for non-CME. For laparoscopic CME the 3- and 5-year cancer-related survival is 87.8–97% and 79.5–80.2%. In stage UICC III the 3- and 5-year cancer-related survival is 83.9% and 80.8% in the Erlangen data of open technique vs. 75.4% and 65.5–71.7% for laparoscopic surgery. For stage UICC III the 3- and 5-year local tumor recurrence is 3.8%. The published data and the results from Erlangen demonstrate that CME is safe in experienced hands with no increased morbidity. It offers an obvious survival benefit for the patients which can be achieved solely by surgery. Teaching programs are needed for minimally invasive CME to facilitate this technique in the same quality compared to open surgery. Passing these challenges CME will become the standard of care for patients with colon carcinomas offering all benefits of minimally invasive surgery and oncological outcome.

Maintenance and break of immune tolerance against human factor VIII in a new transgenic hemophilic mouse model

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3698-3707 ◽  
Author(s):  
Pauline M. van Helden ◽  
Sabine Unterthurner ◽  
Corinna Hermann ◽  
Maria Schuster ◽  
Rafi U. Ahmad ◽  
...  
Keyword(s):  
Factor Viii ◽  
Neutralizing Antibodies ◽  
Basic Research ◽  
Standard Of Care ◽  
Current Therapy ◽  
Current Standard ◽  
Transgenic Mouse Line ◽  
Human Factor Viii ◽  
Immunogenicity Assessment ◽  
Immunogenic Properties

Abstract Replacement of the missing factor VIII (FVIII) is the current standard of care for patients with hemophilia A. However, the short half-life of FVIII makes frequent treatment necessary. Current efforts focus on the development of longer-acting FVIII concentrates by introducing chemical and genetic modifications to the protein. Any modification of the FVIII protein, however, risks increasing its immunogenic potential to induce neutralizing antibodies (FVIII inhibitors), and this is one of the major complications in current therapy. It would be highly desirable to identify candidates with a high risk for increased immunogenicity before entering clinical development to minimize the risk of exposing patients to such altered FVIII proteins. In the present study, we describe a transgenic mouse line that expresses a human F8 cDNA. This mouse is immunologically tolerant to therapeutic doses of native human FVIII but is able to mount an antibody response when challenged with a modified FVIII protein that possesses altered immunogenic properties. In this situation, immunologic tolerance breaks down and antibodies develop that recognize both the modified and the native human FVIII. The applicability of this new model for preclinical immunogenicity assessment of new FVIII molecules and its potential use for basic research are discussed.

Real-world efficacy of bone modifying agents (BMAs) in patients with breast cancer (BC) treated in an academic health system: Use of the “green button.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18054-e18054
Author(s):  
Yasmin Karimi ◽  
Saurabh Gombar ◽  
Latanya Dean ◽  
Jennifer Hansen ◽  
Alison Callahan ◽  
...  
Keyword(s):  
Medical Record ◽  
Real World ◽  
Point Of Care ◽  
Pathologic Fracture ◽  
Standard Of Care ◽  
Cord Compression ◽  
Outcome Data ◽  
Published Data ◽  
Diagnostic Codes ◽  
Skeletal Related Events

e18054 Background: BC patients (pts) have a high incidence of bone metastases (mets) and associated morbidity. BMAs – zoledronic acid (ZA) and denosumab (Den) – reduce bone met related skeletal related events (SREs). ASCO guidelines do not recommend one over another, and survival and real-world outcome data to guide point-of-care decision-making is lacking. We used the previously developed “Green Button” informatics consult service, designed to rapidly test hypotheses when no applicable published data is available to guide treatment choices (Longhurst et al Health Affairs 2014), to compare BMA efficacy in BC patients. Methods: Patients treated for BC at Stanford HealthCare between 2009 - 2018, receiving standard of care cancer and BMA therapy, as determined by their oncologists, were identified who had > 2 electronic health records (EHRs) documenting BMA administration, and had either ICD9 174 or ICD10 C50 diagnostic codes. Pts were grouped into Den only, ZA only, or both. Two outcomes were analyzed: 1) SREs as a composite outcome of pathologic fracture (1st ICD10 M84.5); spinal cord compression (1st ICD10 M47.1 or G95.2), radiation therapy (1st CPT 77300) or hypercalcemia (calcium ≥10.5); and 2) death. Effects were compared relative to baseline treatment with ZA; we show results of log rank tests for differences in survival outcomes. Three analyses were performed: 1) Unadjusted analysis; 2) Basic matching analysis accounting for length of medical record, age, sex and year of treatment; 3) Propensity score matching using all available data; all prior to index treatment with either Den or ZA. Results: 802 patients had ≥ 2 records of BMA administration. Comparison of Den only and ZA only pts is shown in the table below. Median ages and length of medical record were balanced in all groups. Conclusions: This preliminary retrospective analysis of unsupervised BMA use suggests that Den is superior to ZA for the outcomes of interest; confirmatory analyses are underway.[Table: see text]

Comparison of treatment costs of pembrolizumab versus nivolumab in head and neck squamous cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19368-e19368
Author(s):  
Justin Yeh ◽  
Achuta Kumar Guddati
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Average Cost ◽  
Standard Of Care ◽  
Neck Squamous Cell Carcinoma ◽  
Published Data ◽  
Cost Of Treatment ◽  
The Cost

e19368 Background: Pembrolizumab and Nivolumab are PD-1 inhibiting immunotherapy agents approved for the treatment of metastatic or recurrent head and neck squamous cell carcinoma in patients previously treated with platinum-based chemotherapy. Both therapies have demonstrated similar survival benefits and adverse event profiles, but there is no published comparison of treatment cost and survival between the two agents. This study aims to analyze the cost-effectiveness of pembrolizumab compared to nivolumab through network meta-analysis techniques. Methods: Data published from the KEYNOTE-040 (pembrolizumab) and CheckMate 141 (nivolumab) studies were used to generate a model incorporating the cost of each drug in both the arms. The cost of treatment of side effects was extracted from previously published data and used for cost estimation in the model. Data from the standard of care arms (cetuximab, methotrexate, or docetaxel) in each study were adjusted to provide a common reference between the two studies. The number of years added in terms of overall survival was calculated for the entire experimental arm and the cost of each such year was calculated. All costs were adjusted for inflation. Results: Using published data from the KENOTE-040 trial, the average cost per patient adjusted for inflation over time, over 24 months in the pembrolizumab arm was $159,302, and similarly using data from the Checkmate 141 trial, the average cost per patient over 18 months in the nivolumab arm was $118,790. The cost of management of adverse effects was $18,728 vs $16,685 (pembrolizumab vs. nivolumab) during these time periods. Our model suggests that the adjusted total cost per month for patients on these drugs is very similar: $7417.91 vs. $7526.38. Assuming that the quality of life was similar in both groups and using an average OS for the standard of care arms, our model predicts that ICER for pembrolizumab is higher than nivolumab ($203,085 vs. 132,644). Conclusions: Both pembrolizumab and nivolumab improve survival benefit compared to their respective standard of care arms. However, the ICER for both medications is higher than the threshold set by many payers and health provider organizations. The model makes several assumptions which may render it less accurate to compare between trials but the cost of treatment for both drugs is not in the cost-effective range. To utilize these drugs in a cost-conscious practice, further research is needed to investigate lower doses at a slower frequency along with reduction of the price for each medication.

Topical Application of a Gentamicin-Collagen Sponge Combined with Systemic Antibiotic Therapy for the Treatment of Diabetic Foot Infections of Moderate Severity

2012 ◽  
Vol 102 (3) ◽  
pp. 223-232 ◽  
Author(s):  
Benjamin A. Lipsky ◽  
Michael Kuss ◽  
Michael Edmonds ◽  
Alexander Reyzelman ◽  
Felix Sigal
Keyword(s):  
Treatment Group ◽  
Antibiotic Therapy ◽  
Diabetic Foot ◽  
Clinical Cure ◽  
Standard Of Care ◽  
Collagen Sponge ◽  
Control Group ◽  
Moderate Severity ◽  
Diabetic Foot Infections ◽  
Systemic Antibiotic Therapy

Background: The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity. Methods: We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n = 38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped. Results: On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P = .017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P =.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P ≤ .038) and a reduced time to pathogen eradication (P &lt; .001). Safety data were similar for both groups. Conclusions: Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted. (J Am Podiatr Med Assoc 102(3): 223-232, 2012)

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