Trial Outcomes & Findings for TOX NEG Trial: Clostridium Difficile Diagnosis and Treatment (NCT NCT03388268)

NCT ID: NCT03388268

Last Updated: 2021-07-26

Results Overview

Stool specimens will be examined via culture and metagenomic analyses for the presence of detectable C. difficile. Presence will be defined as presence of culturable C. difficile in stool any time after collection of enrollment stool samples.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 15 participants
• Primary outcome timeframe: Through 8 weeks after completion of study drug
• Results posted on: 2021-07-26

Participant Flow

Participant milestones

Measure	Oral Vancomycin 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Overall Study STARTED	8	7
Overall Study COMPLETED	7	4
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

TOX NEG Trial: Clostridium Difficile Diagnosis and Treatment

Baseline characteristics by cohort

Measure	Oral Vancomycin n=8 Participants 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=7 Participants Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Total n=15 Participants Total of all reporting groups
Age, Continuous	66 years n=5 Participants	64 years n=7 Participants	65 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Non-white race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White race	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Receiving antibiotics at enrollment	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through 8 weeks after completion of study drug

Population: 12 of 15 enrolled patients had follow up stool specimens available for analysis. C. difficile was detected in 9 of these 12 during the follow up period.

Stool specimens will be examined via culture and metagenomic analyses for the presence of detectable C. difficile. Presence will be defined as presence of culturable C. difficile in stool any time after collection of enrollment stool samples.

Outcome measures

Measure	Oral Vancomycin n=7 Participants 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=5 Participants Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Number of Participants With Detectable C. Difficile	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Through 8 weeks after completion of study drug

Population: 12 of 15 enrolled patients had follow up environmental swabs available for analysis. C. difficile was detected in 9 of these 12 during the follow up period.

Swabs from participants' home and hospital environments will be examined via culture and metagenomic analyses for the presence and/or persistence of C. difficile and other multidrug resistant organisms.

Outcome measures

Measure	Oral Vancomycin n=7 Participants 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=5 Participants Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Number of Participants With Detectable Environmental Contamination	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Through 8 weeks after completion of study drug

Duration of diarrhea will be compared between groups. Duration of diarrhea will be assessed daily during study drug using a questionnaire and the Bristol Stool Chart. The Bristol Stool Chart measures stool consistency. Diarrhea will be defined as Bristol Stool Chart types 5-7.

Outcome measures

Measure	Oral Vancomycin n=8 Participants 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=7 Participants Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Duration of Diarrhea in Study Participants as Defined by Daily Symptoms and Questionnaire Using the Bristol Stool Chart	2 Days Interval 2.0 to 13.0	4 Days Interval 3.0 to 11.0

SECONDARY outcome

Timeframe: Through 8 weeks after completion of the study drug

Population: 12 of 15 enrolled patients had follow up stool specimens available for analysis. Multidrug organisms were detected in 10 of these 12 during the follow up period.

Stool specimens will be examined via culture and metagenomic analyses for the presence of multidrug resistant organisms before and after study drug.

Outcome measures

Measure	Oral Vancomycin n=7 Participants 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=5 Participants Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Presence of Other Multidrug Resistant Organisms in the Gut Microbiome of Study Participants	6 Participants	4 Participants

Adverse Events

Oral Vancomycin

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oral Vancomycin n=8 participants at risk 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=7 participants at risk Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Endocrine disorders Volume overload	12.5% 1/8 • Number of events 1 • Adverse events were collected through 8 weeks after completion of the study drug.	0.00% 0/7 • Adverse events were collected through 8 weeks after completion of the study drug.
Vascular disorders Hypoxemia	12.5% 1/8 • Number of events 1 • Adverse events were collected through 8 weeks after completion of the study drug.	0.00% 0/7 • Adverse events were collected through 8 weeks after completion of the study drug.

Other adverse events

Measure	Oral Vancomycin n=8 participants at risk 125mg of oral vancomycin four times per day Oral Vancomycin: Oral vancomycin 125mg 4 times per day Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid	Placebo n=7 participants at risk Placebo four times per day Placebo: Sugar liquid manufactured to mimic oral vancomycin 125mg Toxin enzyme immunoassay: EIA assay: Wampole/Tech Lab Tox A/B II Nuceleic acid amplification test: NAAT: Xpert C. difficile, Cepheid
Gastrointestinal disorders Abdominal pain	25.0% 2/8 • Number of events 2 • Adverse events were collected through 8 weeks after completion of the study drug.	0.00% 0/7 • Adverse events were collected through 8 weeks after completion of the study drug.
General disorders Headache, vertigo, nausea/vomiting	0.00% 0/8 • Adverse events were collected through 8 weeks after completion of the study drug.	14.3% 1/7 • Number of events 1 • Adverse events were collected through 8 weeks after completion of the study drug.
General disorders Syncope, altered mental status	12.5% 1/8 • Number of events 1 • Adverse events were collected through 8 weeks after completion of the study drug.	0.00% 0/7 • Adverse events were collected through 8 weeks after completion of the study drug.
Gastrointestinal disorders C. difficile EIA positive stool sample	0.00% 0/8 • Adverse events were collected through 8 weeks after completion of the study drug.	14.3% 1/7 • Number of events 1 • Adverse events were collected through 8 weeks after completion of the study drug.

Additional Information

Kimberly Reske, MPH, Research Coordinator

Washington University in St. Louis

Phone: 314-747-4041

Email: kreske@wustl.edu

Results disclosure agreements

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