Trial Outcomes & Findings for Impact of Oral Antibiotic Treatment on C. Difficile (NCT NCT02057198)

NCT ID: NCT02057198

Last Updated: 2019-10-02

Results Overview

Rodac plates were used to take environmental samples from 5 different sites within each patient's hospital room (bedrail, overbed table, sink, toilet seat, bathroom floor). Each Rodac plate samples a surface area of \~25 cm2. 5 replicates were taken for each site and repeated on days 0, 3, 7, and 14. Median total colony counts are reported for each treatment group. Data from the specified time points were combined to construct a decay slope, representing the reduction in log(CFUs)/day for each treatment group. We compared the slope (rate of change) between treatment groups using mixed effects models.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

33 participants

Primary outcome timeframe

Days 0, 3, 7 and 14.

Results posted on

2019-10-02

Participant Flow

Participant milestones

Participant milestones
Measure
Fidaxomicin
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
125 mg. orally 4 times a day for 10 days Vancomycin
Overall Study
STARTED
11
11
11
Overall Study
COMPLETED
11
10
10
Overall Study
NOT COMPLETED
0
1
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Fidaxomicin
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
125 mg. orally 4 times a day for 10 days Vancomycin
Overall Study
Death
0
0
1
Overall Study
Discharged early; lost to followup
0
1
0

Baseline Characteristics

Impact of Oral Antibiotic Treatment on C. Difficile

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Fidaxomicin
n=11 Participants
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=10 Participants
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=10 Participants
125 mg. orally 4 times a day for 10 days Vancomycin
Total
n=31 Participants
Total of all reporting groups
Age, Continuous
60.6 years
STANDARD_DEVIATION 22 • n=99 Participants
62.2 years
STANDARD_DEVIATION 15.1 • n=107 Participants
63.4 years
STANDARD_DEVIATION 9.6 • n=206 Participants
62 years
STANDARD_DEVIATION 16.1 • n=7 Participants
Sex: Female, Male
Female
4 Participants
n=99 Participants
6 Participants
n=107 Participants
5 Participants
n=206 Participants
15 Participants
n=7 Participants
Sex: Female, Male
Male
7 Participants
n=99 Participants
4 Participants
n=107 Participants
5 Participants
n=206 Participants
16 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
11 Participants
n=99 Participants
10 Participants
n=107 Participants
10 Participants
n=206 Participants
31 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=99 Participants
5 Participants
n=107 Participants
4 Participants
n=206 Participants
14 Participants
n=7 Participants
Race (NIH/OMB)
White
6 Participants
n=99 Participants
5 Participants
n=107 Participants
6 Participants
n=206 Participants
17 Participants
n=7 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Region of Enrollment
United States
11 participants
n=99 Participants
10 participants
n=107 Participants
10 participants
n=206 Participants
31 participants
n=7 Participants

PRIMARY outcome

Timeframe: Days 0, 3, 7 and 14.

Population: Only completed participants were included in the analysis.

Rodac plates were used to take environmental samples from 5 different sites within each patient's hospital room (bedrail, overbed table, sink, toilet seat, bathroom floor). Each Rodac plate samples a surface area of \~25 cm2. 5 replicates were taken for each site and repeated on days 0, 3, 7, and 14. Median total colony counts are reported for each treatment group. Data from the specified time points were combined to construct a decay slope, representing the reduction in log(CFUs)/day for each treatment group. We compared the slope (rate of change) between treatment groups using mixed effects models.

Outcome measures

Outcome measures
Measure
Fidaxomicin
n=11 Participants
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=10 Participants
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=10 Participants
125 mg. orally 4 times a day for 10 days Vancomycin
Change in Total Median Total Colony Forming Units (CFU) of C. Difficile Identified in the Hospital Room Environment for Each Antibiotic Treatment Group.
Day 14
0 Colony forming units (CFUs)
Interval 0.0 to 0.0
0 Colony forming units (CFUs)
Interval 0.0 to 0.0
0 Colony forming units (CFUs)
Interval 0.0 to 0.0
Change in Total Median Total Colony Forming Units (CFU) of C. Difficile Identified in the Hospital Room Environment for Each Antibiotic Treatment Group.
Day 0
56 Colony forming units (CFUs)
Interval 0.0 to 158.0
33 Colony forming units (CFUs)
Interval 23.0 to 43.0
149 Colony forming units (CFUs)
Interval 0.0 to 227.0
Change in Total Median Total Colony Forming Units (CFU) of C. Difficile Identified in the Hospital Room Environment for Each Antibiotic Treatment Group.
Day 3
7 Colony forming units (CFUs)
Interval 4.0 to 9.0
53 Colony forming units (CFUs)
Interval 17.0 to 92.0
24 Colony forming units (CFUs)
Interval 5.0 to 43.0
Change in Total Median Total Colony Forming Units (CFU) of C. Difficile Identified in the Hospital Room Environment for Each Antibiotic Treatment Group.
Day 7
0 Colony forming units (CFUs)
Interval 0.0 to 0.0
15 Colony forming units (CFUs)
Interval 12.0 to 18.0
0 Colony forming units (CFUs)
Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Days 0, 3, 7, and 14

Population: Only completed participants were included in the analysis.

In addition to total colony counts over time, the investigators also assessed the proportion of positive cultures over time (from the 5 replicate Rodac plate samplings repeated at each of 5 sites within each patient room: bedrail, overbed table, sink, toilet seat and bathroom floor). The cumulative proportion of positive cultures (including days 0, 3, 7, 14) is reported according to each treatment group.

Outcome measures

Outcome measures
Measure
Fidaxomicin
n=794 Environmental cultures
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=575 Environmental cultures
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=774 Environmental cultures
125 mg. orally 4 times a day for 10 days Vancomycin
Total Environmental Contamination According to Antibiotic Treatment Group
13.4 percentage of positive cultures
18.6 percentage of positive cultures
7.6 percentage of positive cultures

SECONDARY outcome

Timeframe: Days 0-14

Population: Ribotyping could only be conducted in instances where sufficient growth occurred from both patient and environmental samples to permit subculture.

When sufficient growth was available to permit sub-culture and ribotyping, we conducted ribotyping of each patient's stool C. difficile isolate for comparison to isolates from the same patient's hospital environment. Reported is the total percent of hospital room environmental isolates that match the ribotyping of the associated patient's stool sample (there is no averaging).

Outcome measures

Outcome measures
Measure
Fidaxomicin
n=22 Environmental Isolates
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=25 Environmental Isolates
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=9 Environmental Isolates
125 mg. orally 4 times a day for 10 days Vancomycin
Molecular Relatedness of Isolates
68.1 percent of matching isolates
80.0 percent of matching isolates
77.8 percent of matching isolates

SECONDARY outcome

Timeframe: Days 0, 3, 7, 14

Population: Only completed participants were included in the analysis.

C. difficile was isolated and serially diluted to permit colony counts (CFU/g stool) over time for each patient.

Outcome measures

Outcome measures
Measure
Fidaxomicin
n=11 Participants
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=10 Participants
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=10 Participants
125 mg. orally 4 times a day for 10 days Vancomycin
C. Difficile Shedding in Stool Over Time
Day 0
815940 CFU/g stool
Standard Deviation 949503
2233564 CFU/g stool
Standard Deviation 3845558
35340 CFU/g stool
Standard Deviation 41612
C. Difficile Shedding in Stool Over Time
Day 3
72200 CFU/g stool
Standard Deviation 156429
1200 CFU/g stool
Standard Deviation 283
400 CFU/g stool
Standard Deviation 693
C. Difficile Shedding in Stool Over Time
Day 7
0 CFU/g stool
Standard Deviation 0
0 CFU/g stool
Standard Deviation 0
0 CFU/g stool
Standard Deviation 0
C. Difficile Shedding in Stool Over Time
Day 14
0 CFU/g stool
Standard Deviation 0
0 CFU/g stool
Standard Deviation 0
0 CFU/g stool
Standard Deviation 0

SECONDARY outcome

Timeframe: Days 0, 3, 7, 14

Population: Only completed participants were included in the analysis.

Count of stool cultures positive for C. difficile at each time point

Outcome measures

Outcome measures
Measure
Fidaxomicin
n=20 specimens
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=22 specimens
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=20 specimens
125 mg. orally 4 times a day for 10 days Vancomycin
Count of Stool Specimens From Patients That Are Positive for C. Difficile
Day 0
20 Number of positive stool cultures
21 Number of positive stool cultures
17 Number of positive stool cultures
Count of Stool Specimens From Patients That Are Positive for C. Difficile
Day 3
6 Number of positive stool cultures
3 Number of positive stool cultures
2 Number of positive stool cultures
Count of Stool Specimens From Patients That Are Positive for C. Difficile
Day 7
0 Number of positive stool cultures
0 Number of positive stool cultures
0 Number of positive stool cultures
Count of Stool Specimens From Patients That Are Positive for C. Difficile
Day 14
0 Number of positive stool cultures
0 Number of positive stool cultures
0 Number of positive stool cultures

SECONDARY outcome

Timeframe: Days 0, 3, 7, 14

Population: Only completed participants were included in the analysis.

Percentage of stool cultures positive for C. difficile at each time point

Outcome measures

Outcome measures
Measure
Fidaxomicin
n=20 specimens
200 mg. 2 times a day for 10 days Fidaxomicin
Metronidazole
n=22 specimens
500 mg.orally 3 times daily for 10 days Metronidazole
Vancomycin
n=20 specimens
125 mg. orally 4 times a day for 10 days Vancomycin
Percentage of Stool Specimens From Patients That Are Positive for C. Difficile
Day 0
100 % of positive stool cultures
95.5 % of positive stool cultures
85 % of positive stool cultures
Percentage of Stool Specimens From Patients That Are Positive for C. Difficile
Day 3
60 % of positive stool cultures
75 % of positive stool cultures
33 % of positive stool cultures
Percentage of Stool Specimens From Patients That Are Positive for C. Difficile
Day 7
0 % of positive stool cultures
0 % of positive stool cultures
0 % of positive stool cultures
Percentage of Stool Specimens From Patients That Are Positive for C. Difficile
Day 14
0 % of positive stool cultures
0 % of positive stool cultures
0 % of positive stool cultures

Adverse Events

Fidaxomicin

Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths

Metronidazole

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Vancomycin

Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Daniel Sexton, M.D.

Duke University Medical Center

Phone: 919-684-4596

Results disclosure agreements

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