Clostridium Difficile InfectionPhase 3NCT01987895

Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile - Associated Diarrhea

A Phase 3 study testing Cadazolid and Vancomycin in people with Clostridium Difficile Infection, run by Actelion.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Clostridium Difficile Infection
What is being tested?: Cadazolid and Vancomycin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 632 participants
Where: No sites listed yet
Study dates: 27 Mar 2014to 24 Mar 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed Informed Consent.
Male or female ≥ 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception.
Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with > 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization.

Who cannot join

More than one previous episode of CDAD in the 3-month period prior to randomization.
Evidence of life-threatening or fulminant CDAD.
Likelihood of death within 72 hours from any cause.
History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea.
Antimicrobial treatment active against CDAD administered for > 24 hours except for metronidazole treatment failures (MTF)
Known hypersensitivity or contraindication to study drugs, oxazolidinones, or quinolones.
Unable or unwilling to comply with all protocol requirements.
Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

About this study

Official title: A Multi-center, Randomized, Double-blind Study to Compare the Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile-associated Diarrhea (CDAD)

This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).

Read the detailed description

Subjects selected to participate in the study are treated either with cadazolid or vancomycin for 10 days. At the end of treatment, clinical cure is assessed; subjects are then followed-up to assess any disease recurrence.

Conditions: Clostridium Difficile Infection
Being tested: Cadazolid, Vancomycin, Cadazolid-matching placebo, Vancomycin-matching placebo
Keywords: Post-antibiotic diarrhea, Clostridium difficile infection
Medical subject headings: Clostridium Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CadazolidDrug
Also called ACT-179811
Cadazolid 250 mg as oral suspension twice daily.
VancomycinDrug
Also called Vancocin
Vancomycin 125 mg as oral capsules 4 times daily.
Cadazolid-matching placeboDrug
Placebo matching cadazolid and administered orally twice daily
Vancomycin-matching placeboDrug
Placebo capsules matching vancomycin and administered orally 4 times per day

Study groups in NCT01987895
Study group	Role	What they receive
Cadazolid	Experimental	Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days Receives: Drug: Cadazolid; Drug: Vancomycin-matching placebo
Vancomycin	Active comparator	Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days Receives: Drug: Vancomycin; Drug: Cadazolid-matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population
Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT.
CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.
Measured: Up to Day 12 on average (end-of-treatment + 2 days)
Clinical Cure Rate (CCR) in the Per-protocol Population
Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.
Measured: Up to Day 12 on average (end-of-treatment + 2 days)

Secondary outcomes (3)

Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population
Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The main analysis is performed on the modified intent-to-treat set (mITT).
Measured: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Kaplan-Meier Estimates for Resolution of Diarrhea
Resolution of Diarrhea (ROD) is defined as no more than 3 unformed bowel movements per day for at least two consecutive days for subjects on study treatment.
The Kaplan-Meier estimates (KM estimates) for having an event (ROD) are reported for each time point.
Measured: Up to Day 10
Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores
CDI-DaySyms PRO is a questionnaire assessing 10 symptoms relevant to subjects with CDAD and grouped into 3 domains: Diarrhea symptoms, Abdominal symptoms and Systemic/Other. The subjects rate the severity of each item as None, Mild, Moderate, Severe or Very severe, converted to numeric scores from 0 to 4, respectively. The daily domain score is calculated as the mean of the non-missing responses for that domain on that day. A negative value for change from baseline corresponds to an improvement in domain score. The three domains are evaluated in a hierarchical manner, starting with Diarrhea Symptoms, then Abdominal Symptoms, and finally Systemic/Other Symptoms. The least squares means (LSM) are computed on the scores.
Measured: Day 1 (baseline) and Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Mar 201424 Mar 2017

First posted20 Nov 2013 (estimated)
Study start27 Mar 2014
Primary completion26 Feb 2017
Study completion24 Mar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 632 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01987895
Sponsor's protocol ID: AC-061A301
Status last verified: Jan 2025
First submitted: 7 Nov 2013
Last updated: 4 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Gerding DN, Cornely OA, Grill S, Kracker H, Marrast AC, Nord CE, Talbot GH, Buitrago M, Gheorghe Diaconescu I, Murta de Oliveira C, Preotescu L, Pullman J, Louie TJ, Wilcox MH. Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. Lancet Infect Dis. 2019 Mar;19(3):265-274. doi: 10.1016/S1473-3099(18)30614-5. Epub 2019 Jan 29.
PubMed 30709665
Kleinman L, Talbot GH, Hunsche E, Schuler R, Nord CE. The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection. Value Health. 2018 Apr;21(4):441-448. doi: 10.1016/j.jval.2017.08.3017. Epub 2017 Nov 7.
PubMed 29680101

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingObservational study
Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
Clostridioides Difficile Infection
Active, not recruitingPhase 2
Autologous Fecal Microbiota Transplantation (Auto-FMT) for Prophylaxis of Clostridium Difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
RecruitingEarly Phase 1
Prevention of Recurrence of Clostridioides Difficile Colitis With Ursodeoxycholic Acid (UCDA) as a Supplement to Standard Therapy
Clostridioides Difficile Infection

All Clostridium Difficile Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-center, Randomized, Double-blind Study to Compare the Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile-associated Diarrhea (CDAD)
ClinicalTrials.gov ID: NCT01987895
Acronym / sponsor ID: AC-061A301
Conditions: Clostridium Difficile Infection
Keywords: Post-antibiotic diarrhea, Clostridium difficile infection
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 632 participants (actual)
Lead sponsor: ActelionIndustry (pharma, biotech, devices)
Study start: 27 Mar 2014 (actual)
Primary completion: 26 Feb 2017 (actual)
Study completion: 24 Mar 2017 (actual)
First posted: 20 Nov 2013 (estimated)
Results: Posted 4 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Cadazolid	Experimental	Drug: Cadazolid, Drug: Vancomycin-matching placeboSubjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Vancomycin	Active comparator	Drug: Vancomycin, Drug: Cadazolid-matching placeboSubjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Signed Informed Consent.
Male or female ≥ 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception.
Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with > 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization.

Key exclusion criteria (8 listed)

More than one previous episode of CDAD in the 3-month period prior to randomization.
Evidence of life-threatening or fulminant CDAD.
Likelihood of death within 72 hours from any cause.
History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea.
Antimicrobial treatment active against CDAD administered for > 24 hours except for metronidazole treatment failures (MTF)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CadazolidAlso: ACT-179811Cadazolid 250 mg as oral suspension twice daily.	Drug	Cadazolid
VancomycinAlso: VancocinVancomycin 125 mg as oral capsules 4 times daily.	Drug	Vancomycin
Cadazolid-matching placeboPlacebo matching cadazolid and administered orally twice daily	Drug	Vancomycin
Vancomycin-matching placeboPlacebo capsules matching vancomycin and administered orally 4 times per day	Drug	Cadazolid

Primary outcome

Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population
Time frame: Up to Day 12 on average (end-of-treatment + 2 days)
Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.
Clinical Cure Rate (CCR) in the Per-protocol Population
Time frame: Up to Day 12 on average (end-of-treatment + 2 days)
Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.

3 secondary outcomes

Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population
Time frame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Kaplan-Meier Estimates for Resolution of Diarrhea
Time frame: Up to Day 10
Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores
Time frame: Day 1 (baseline) and Day 3

Results and safety

Results posted to the registry on 4 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cadazolid	306	276
Vancomycin	326	296

Primary outcome: Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population

Time frame: Up to Day 12 on average (end-of-treatment + 2 days). Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Cadazolid n = 302	Vancomycin n = 318
Value	83.8 (79.2 to 87.5)	85.2 (80.9 to 88.7)

Cadazolid vs Vancomycin: Difference between 2 proportions: -1.4 (95% CI -7.2 to 4.3)
Cadazolid vs Vancomycin: Difference between 2 proportions: -2.4 (95% CI -8.1 to 3.2)

Population analysed: All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD.

Primary outcome: Clinical Cure Rate (CCR) in the Per-protocol Population

Time frame: Up to Day 12 on average (end-of-treatment + 2 days). Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Cadazolid n = 282	Vancomycin n = 288
Value	87.6 (83.2 to 90.9)	91.7 (87.9 to 94.3)

Cadazolid vs Vancomycin: Difference between 2 proportions: -4.1 (95% CI -9.2 to 1.0)

Population analysed: All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD and without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious and frequent adverse events are reported from study treatment initiation up to Day 17 on average (i.e., 7 days after end-of-treatment or study withdrawal) and all-cause mortality up to Day 40 on average (i.e. 28 to 32 days after end-of-treatment or study withdrawal). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cadazolid	19 of 304 (6.3%)	33 of 304 (10.9%)	7 of 304
Vancomycin	26 of 322 (8.1%)	49 of 322 (15.2%)	7 of 322

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30709665Gerding DN, Cornely OA, Grill S, Kracker H, Marrast AC, Nord CE, Talbot GH, Buitrago M, Gheorghe Diaconescu I, Murta de Oliveira C, Preotescu L, Pullman J, Louie TJ, Wilcox MH. Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. Lancet Infect Dis. 2019 Mar;19(3):265-274. doi: 10.1016/S1473-3099(18)30614-5. Epub 2019 Jan 29.
Derived from this study: PubMed 29680101Kleinman L, Talbot GH, Hunsche E, Schuler R, Nord CE. The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection. Value Health. 2018 Apr;21(4):441-448. doi: 10.1016/j.jval.2017.08.3017. Epub 2017 Nov 7.

Related trials for Clostridium Difficile Infection

Not yet recruitingObservational study
Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
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Active, not recruitingObservational study
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RecruitingPhase 3
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Anne Claire Marrast, MD study director

Actelion

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cadazolid and Vancomycin in people with Clostridium Difficile Infection, run by Actelion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population (time frame: Up to Day 12 on average (end-of-treatment + 2 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01987895, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.