Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00261807|
Recruitment Status : Completed
First Posted : December 5, 2005
Last Update Posted : March 16, 2018
Daptomycin is a new antimicrobial agent which has activity against resistant Gram positive cocci including MRSA. The phase 3 clinical trials for skin and soft tissue infections (SSTI) with Staphylococci and Streptococci have already demonstrated that daptomycin was noninferior to the comparator agent (vancomycin or beta-lactams) (10). Although this clinical trial did not include any patients with clostridial infection, there is in vitro data to support the activity of daptomycin against a variety of clostridial species(11) ( Clostridium perfringens) Therefore, for this trial we will include patients with clostridial infections with this species. Additionally, the patients in the SSTI study were not as ill as the proposed study population. Therefore for treatment of such severe infections, we would like to use a higher dose of daptomycin (6mg/kg/dose). The reasons for using a higher dose of daptomycin in this subgroup are as follows:
- Patients who are severely ill have an increased volume of distribution; and therefore have a lower serum concentration of daptomycin. These patients might require a higher dose of daptomycin to achieve the desired serum concentration.
- One of the organisms involved in necrotizing fasciitis is enterococcus (both-fecalis and faecium). E.faecium has higher MICs to daptomycin and would require a higher dose of the drug to achieve adequate free (unbound) serum concentration of the drug.
- Both necrotizing fasciitis and endocarditis are serious deep seated infections. The clinical trials for endocarditis are using 6mg/kg/dose of daptomycin.
Therefore for optimal treatment of necrotizing fasciitis, it is justifiable that we should use the higher dose of daptomycin.
To evaluate the clinical and microbiological efficacy and safety of higher dose daptomycin therapy in the treatment of patients with severe necrotizing skin and soft tissue infections.
Type of Study:
Open label, single center study.
|Condition or disease||Intervention/treatment||Phase|
|Fasciitis, Necrotizing Severe Necrotizing Skin and Soft Tissue Infections Fournier's Gangrene||Drug: Daptomycin 6mg/kg/day||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open Label, Single Center Study to Evaluate Higher Doses of Daptomycin in the Treatment of Patients With Severe Necrotizing Skin and Soft Tissue Infections.|
|Study Start Date :||June 2005|
|Actual Primary Completion Date :||May 2008|
|Actual Study Completion Date :||May 2008|
Single ARM Study
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections.
|Drug: Daptomycin 6mg/kg/day|
- Clinical Response to High Dose Daptomycin Therapy [ Time Frame: The clinical response will be measured at the end of treatment (7-14 days) and test of cure (3-28 days) post end of treatment): ]The signs, symptoms labs measured for resolution of disease were: pain out of proportion, tenderness to palpation, elevated temps (100.4) or reduced temp. (>96), WBC counts > 12,00/cu.mm, swelling, erythema, induration, pus formation. The clinical response was documented as: cure (resolution of clinical significant signs and symptoms and no additional gram-positive antibiotic therapy is needed ;improved, (partial resolution of clinical signs and symptoms (although patient's clinical status has not completely returned to preinfection baseline, infectious process has been controlled , no additional gram-positive antibiotic therapy is needed; failure (no response worsening of clinical signs, symptoms of infection; or additional gram-positive antibiotic therapy is needed ); or unable to evaluate (unable to determine response; e.g., no evaluation performed at time of point, or administration of non-study antibiotics effective against study pathogen).
- Microbiology Response to High-Dose Daptomycin Therapy [ Time Frame: The microbiologicall response will be measured at the end of treatment (7-14 days) and test of cure (3-28 days) post end of treatment): ]Bacterial cultures were obtained in all patients and repeated if the patient had a second surgical intervention. The microbiological response was as follows: Documented Eradicated: the baseline infecting pathogen was absent at end of treatment as determined by a negative culture. Presumed Eradicated: The baseline infection was presumed absent at the end of treatment as determined that there was "nothing to culture". Documented Persistent: The baseline infecting pathogen was present at the end of treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00261807
|United States, Maryland|
|R Adams Cowley Shock Trauma Center, U. of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Manjari G Joshi, MD||University of Maryland, School of Medicine - Shock Trauma|