Open Label, Single Center Study to Evaluate Higher Doses of Daptomycin in the Treatment of Patients With Severe Necrotizing Skin and Soft Tissue Infections.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
研究概览
简要总结
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.
Objective:
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.
详细描述
At the shock trauma center, the management of patients with NSTI is conducted in the following fashion: All new patients with NSTI are admitted to the trauma center through the 12-bed shock trauma admitting area. Full hemodynamic resuscitation is undertaken. The on-call soft-tissue and infection team is mobilized. Standard investigations, radiographic evaluations, and laboratory tests, including gram stain and culture specimens, are obtained. The University of Maryland Medical Systems/shock trauma laboratory is utilized for hematology, biochemical, and bacteriologic studies. Aggressive empiric broad-spectrum antibiotic therapy is instituted. The standard antibiotic therapy for NSTI's at shock trauma includes the following:
Gram negative rods: Piperacillin/Tazobactam or quinolones or aztreonam /
- aminoglycosides Anaerobes: Piperacillin/Tazobactam or Metronidazole or Clindamycin Gram positive cocci (not MRSA/VRE): Piperacillin/Tazobactam or Clindamycin Gram positive cocci (MRSA): Vancomycin Gram positive cocci (VRE): Linezolid For purposes of this study, daptomycin would replace Vancomycin, Linezolid or clindamycin for gram positive coverage. Prior antibiotic therapy, culture data, comorbid conditions, allergy history and other variables may result in institution of a different antibiotic regimen.
The patient is taken to the shock trauma operating room for debulking of infected tissue (excision and debridement) and reculturing. Postoperatively, the patient is moved to a critical or intensive care unit for further management and monitoring. When the patient is stable, HBO is begun within 12 hours of arrival. Once the patient is enrolled in the study the following procedures will be followed:
Antibiotic Therapy:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Single ARM Study
It was a single arm study with higher dose of daptomycin used for patients with severe skin and soft tissue infections.
干预措施: Daptomycin 6mg/kg/day (Drug)
结局指标
主要结局
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
时间窗: The clinical response was measured at the end of treatment (7-14 days)
Clinical response was assessed by measuring impact of therapy on certain wound parameters. Specifically Erythema, Induration/Swelling, Suppuration, were recorded visually and WBC Counts were considered improved if \<12,000/cu mm. The clinical response was documented as: 1. CURE (resolution of clinical signs and symptoms and no additional need for gram-positive antibiotic therapy. 2. IMPROVED (partial resolution of clinical signs and symptoms (although patient's clinical status had not completely returned to preinfection baseline but infectious process had been controlled , no additional gram-positive antibiotic therapy was needed; 3. FAILURE (no response, worsening of clinical signs and symptoms of infection; or additional gram-positive antibiotic therapy was needed ); 4. UNABLE TO EVALUATE (unable to determine response; e.g., no evaluation performed at specified time points, or administration of non-study antibiotics effective against study pathogen).
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
时间窗: The clinical response was measured at Test of Cure (3-28 days post end of treatment)
Clinical response was assessed by measuring impact of therapy on certain wound parameters. Specifically Erythema, Induration/Swelling, Suppuration, were recorded visually and WBC Counts were considered improved if \<12,000/cu mm. The clinical response was documented as: 1. CURE (resolution of clinical signs and symptoms and no additional need for gram-positive antibiotic therapy. 2. IMPROVED (partial resolution of clinical signs and symptoms (although patient's clinical status had not completely returned to preinfection baseline but infectious process had been controlled , no additional gram-positive antibiotic therapy was needed; 3. FAILURE (no response, worsening of clinical signs and symptoms of infection; or additional gram-positive antibiotic therapy was needed ); 4. UNABLE TO EVALUATE (unable to determine response; e.g., no evaluation performed at specified time points, or administration of non-study antibiotics effective against study pathogen).
次要结局
- Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)(The microbiologicall response will be measured at the end of treatment (7-14 days) and Test of Cure (TOC) (3-28 days))
研究者
Denise Rudell
Program Manager for Dr. Manjari Joshi
University of Maryland, Baltimore