Trial Outcomes & Findings for Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections (NCT NCT00261807)

NCT ID: NCT00261807

Last Updated: 2022-01-27

Results Overview

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).

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

25 participants

Primary outcome timeframe

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

Results posted on

2022-01-27

Participant Flow

Patients were enrolled from an academic inpatient center which sees about 200 severe soft tissue patients every year. Subjects were enrolled from (2005-2008).

Patients with necrotizing skin infections were screened for the study. A total of 25 subjects were enrolled. Patients were excluded if they had renal failure, high CPK, or myoglobln or if they did not meet the inclusion exculsion criteria. Also, if patient was unable to give consent and family was not present.

Participant milestones

Participant milestones
Measure
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. Daptomycin 6mg/kg/day
Overall Study
STARTED
25
Overall Study
COMPLETED
18
Overall Study
NOT COMPLETED
7

Reasons for withdrawal

Reasons for withdrawal
Measure
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. Daptomycin 6mg/kg/day
Overall Study
Lost to Follow-up
2
Overall Study
Adverse Event
2
Overall Study
Death
1
Overall Study
Protocol Violation
2

Baseline Characteristics

Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Single ARM Study
n=25 Participants
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections. Daptomycin 6mg/kg/day
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
23 Participants
n=5 Participants
Age, Categorical
>=65 years
2 Participants
n=5 Participants
Sex: Female, Male
Female
7 Participants
n=5 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
13 Participants
n=5 Participants
Race (NIH/OMB)
White
12 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
25 participants
n=5 Participants
WBC Counts,Fever and Wound Appearance.
25 participants
n=5 Participants

PRIMARY outcome

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

Population: Of the total 25 patients enrolled, 18 were measured as described in Baseline Population

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).

Outcome measures

Outcome measures
Measure
Single ARM Study
n=18 Participants
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections. Daptomycin 6mg/kg/day
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Erythema-EOT · Cure
16 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Erythema-EOT · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Erythema-EOT · Failure
2 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Erythema-EOT · Unable to Evaluate
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Induration EOT · Cure
17 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Induration EOT · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Induration EOT · Failure
1 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Induration EOT · Unable to Evaluate
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Suppuration-EOT · Cure
13 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Suppuration-EOT · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Suppuration-EOT · Failure
5 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
Suppuration-EOT · Unable to Evaluate
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
WBC Counts EOT · Cure
18 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
WBC Counts EOT · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
WBC Counts EOT · Failure
0 Participants
Clinical Response to High Dose Daptomycin Therapy at End of Treatment (EOT)
WBC Counts EOT · Unable to Evaluate
0 Participants

PRIMARY outcome

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

Population: Of the total 25 patients enrolled, 18 were measured as described in Baseline Population

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).

Outcome measures

Outcome measures
Measure
Single ARM Study
n=18 Participants
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections. Daptomycin 6mg/kg/day
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Erythema-TOC · Cure
18 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Erythema-TOC · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Erythema-TOC · Failure
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Erythema-TOC · Unable to Evaluate
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Induration TOC · Cure
18 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Induration TOC · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Induration TOC · Failure
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Induration TOC · Unable to Evaluate
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Suppuration · Cure
18 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Suppuration · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Suppuration · Failure
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
Suppuration · Unable to Evaluate
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
WBC Counts-TOC · Cure
18 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
WBC Counts-TOC · Improved
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
WBC Counts-TOC · Failure
0 Participants
Clinical Response to High Dose Daptomycin Therapy at Test of Cure (TOC)
WBC Counts-TOC · Unable to Evaluate
0 Participants

SECONDARY outcome

Timeframe: The microbiologicall response will be measured at the end of treatment (7-14 days) and Test of Cure (TOC) (3-28 days)

Population: Of the 25 patients enrolled in study, 23 were analyzed for Microbiological response at end of treatment and only 18 analyzed at Test of Cure visit (2 lost to follow up, 2 received additional antibiotics for infections at other sites (unrelated to primary infection) and 1 patient died during the study period)

Bacterial cultures were obtained in all patients and repeated if the patient had a second surgical intervention. The microbiological responses were documented as follows: 1. DOCUMENTED ERADICATED: the baseline infecting pathogen was absent at end of treatment as determined by a negative culture. 2. PRESUMED ERADICATED: The baseline infection was presumed absent at the end of treatment as determined that there was "nothing to culture". 3. DOCUMENTED PERSISTENT: The baseline infecting pathogen was present at the end of treatment.

Outcome measures

Outcome measures
Measure
Single ARM Study
n=23 Participants
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections. Daptomycin 6mg/kg/day
Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)
End of Therapy · Documented Eradicated
0 Participants
Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)
End of Therapy · Presumed Eradicated
23 Participants
Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)
End of Therapy · Documented Persistent
0 Participants
Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)
Test of Cure · Documented Eradicated
0 Participants
Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)
Test of Cure · Presumed Eradicated
18 Participants
Microbiological Response to High Dose Daptomycin Therapy at End of Treatment (EOT) and Test of Cure (TOC)
Test of Cure · Documented Persistent
0 Participants

Adverse Events

Single ARM Study

Serious events: 1 serious events
Other events: 9 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Single ARM Study
n=25 participants at risk
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections. Daptomycin 6mg/kg/day
Infections and infestations
Gram Negative Rod Bacteremia
4.0%
1/25 • Number of events 1 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions

Other adverse events

Other adverse events
Measure
Single ARM Study
n=25 participants at risk
It was a single arm study with daptomycin use at a higher dose for patients with severe skin and soft tissue infections. Daptomycin 6mg/kg/day
Infections and infestations
C. difficle infection
4.0%
1/25 • Number of events 1 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions
Infections and infestations
Vaginal Yeast Infection
8.0%
2/25 • Number of events 2 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions
Blood and lymphatic system disorders
Anemia
12.0%
3/25 • Number of events 3 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions
Skin and subcutaneous tissue disorders
Rash
4.0%
1/25 • Number of events 1 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders
Swelling
4.0%
1/25 • Number of events 1 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions
General disorders
High CPK
4.0%
1/25 • Number of events 1 • From initiation of study until Test of Cure (defined as 3-28 days from end of treatment, which was an average duration of 9.4 days of therapy, with a range between 7 and 14 days)
Events described consistent with clinicaltrials.gov definitions

Additional Information

Dr. Manjari Joshi

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

Phone: 410-328-3656

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place