Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections

NCT00261807 | Completed Results

• 1 other identifier: H-26386
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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:

1. 1.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.
2. 2.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.
3. 3.Both necrotizing fasciitis and endocarditis are serious deep seated infections. The clinical trials for endocarditis are using 6mg/kg/dose of daptomycin.

Conditions

Fasciitis, Necrotizing; Severe Necrotizing Skin and Soft Tissue Infections; Fournier's Gangrene

Keywords

severe; skin; infections

Outcome Measures

Primary Outcomes (2)

• Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)

  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).

  The clinical response was measured at the end of treatment (7-14 days)

• Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)

  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).

  The clinical response was measured at Test of Cure (3-28 days post end of treatment)

Secondary Outcomes (1)

• 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)

Study Arms (1)

Single ARM Study

OTHER

It was a single arm study with higher dose of daptomycin used for patients with severe skin and soft tissue infections.

Drug: Daptomycin 6mg/kg/day

Interventions

Daptomycin 6mg/kg/day DRUG

Single ARM Study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Read and sign the consent form. If patient is unable to sign, the consent will be obtained from a legally authorized representative.
• Male or female \> 18 years of age
• If female of child bearing potential, negative pregnancy test
• Surgical diagnosis of severe necrotizing fasciitis, severe necrotizing skin and soft tissue infections (e.g. Fournier's gangrene)
• A) At least three of the following clinical signs and symptoms of local infection should be present:
• pain out of proportion to clinical findings
• tenderness to palpation
• swelling
• erythema
• induration
• pus formation
• B) At least 1 of the two systemic conditions should be present:
• Elevated temps.\[100.4\] or reduced temps. \[\<96\]
• WBC counts \> 12.00/cu.mm
• Positive gram stain or wound culture obtained within 3 calendar days prior to the first dose of Daptomycin.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): collaborator

Study Sites (1)

R Adams Cowley Shock Trauma Center, U. of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Fasciitis, Necrotizing; Soft Tissue Infections; Fournier Gangrene; Lymphoma, Follicular; Infections

Interventions

Daptomycin

Condition Hierarchy (Ancestors)

Fasciitis; Musculoskeletal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Manjari Joshi
• Organization: U. of Maryland Medical Systems, R Adams Cowley Shock Trauma Center

mjoshi@som.umaryland.edu

410-328-3656

Study Officials

• Manjari G Joshi, MD

  University of Maryland, School of Medicine - Shock Trauma

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Program Manager for Dr. Manjari Joshi

Study Record Dates

• First Submitted: December 1, 2005
• First Posted: December 5, 2005
• Study Start: June 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: January 27, 2022
• Results First Posted: March 26, 2021

Record last verified: 2022-01

Locations

US (1)