Clostridium Difficile-Associated Diarrhea (CDAD)Phase 3DEFLECT-1NCT01691248
Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)
A Phase 3 study testing fidaxomicin in people with Clostridium Difficile-Associated Diarrhea (CDAD), run by Optimer Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
Trial summary
The objective of this study is to demonstrate the efficacy and safety of Fidaxomicin versus placebo for prophylaxis against Clostridium difficile-Associated Diarrhea (CDAD) in adult participants undergoing hematopoietic stem cell transplantation (HSCT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile-Associated Diarrhea (CDAD)
- What is being tested?
- fidaxomicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 611 participants
- Where
- No sites listed yet
- Study dates
- 10 Oct 2012to 16 Apr 2015
- 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
- Male or female 18 years of age or older.
- Females of childbearing potential must be using an adequate and reliable method of contraception (e.g., abstinence, barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Males and females must agree to avoid conception during treatment and for four weeks following the end of study treatment.
- Is undergoing HSCT with planned Fluoroquinolone prophylaxis.
- Informed consent is provided.
Who cannot join
- Ongoing active CDAD infection (as evidenced by clinical signs of diarrhea along with the presence of either toxin A and/or B [or their respective genes, tcdA and/or tcdB] of C. difficile in the stool) or current treatment for CDAD.
- Undergoing cord blood transplants.
- Has fulminant colitis, toxic megacolon, or ileus.
- A history of inflammatory bowel disease (ulcerative colitis or Crohn's disease).
- Women who are pregnant or are actively breast feeding (all women of childbearing potential must have a negative pregnancy test result prior to dosing study drug).
- Use of any drugs potentially useful in the treatment of CDAD (e.g. oral Vancomycin, Metronidazole, oral Bacitracin, Fusidic Acid, Rifaximin, and Nitazoxanide).
- Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant in the study, would make it unlikely for the participant to complete the study, or would confound the results of the study.
- Participation in other clinical research studies utilizing an investigational agent within one month prior to screening and during the study treatment period.
About this study
Official title: DEFLECT-1: A Phase 3b Multi-Center, Double-Blind, Randomized, Placebo Controlled Study to Demonstrate the Safety and Efficacy of Fidaxomicin for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation
The objective of this study is to demonstrate the efficacy and safety of Fidaxomicin versus placebo for prophylaxis against Clostridium difficile-Associated Diarrhea (CDAD) in adult participants undergoing hematopoietic stem cell transplantation (HSCT). The primary hypothesis is that Fidaxomicin is superior to placebo in preventing CDAD in participants undergoing HSCT.
- Being tested
- fidaxomicin, Placebo
- Keywords
- Clostridium difficile, Clostridium difficile-Associated Diarrhea, Prophylaxis, Hematopoietic Stem Cell Transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fidaxomicinDrug
Also called DIFICID, DIFICLIR, OPT-80, PAR-101
Fidaxomicin 200 mg tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Study drug treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later).
Study drug treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.
PlaceboDrug
Placebo tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later).
Treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.
| Study group | Role | What they receive |
|---|---|---|
| Fidaxomicin | Active comparator | 200 mg Fidaxomicin tablet once daily for no longer than 40 days Receives: Drug: fidaxomicin |
| Placebo | Placebo comparator | Placebo tablet once daily for no longer than 40 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
Measured: Up to 30 days post-treatment
Secondary outcomes (2)
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment.
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
Measured: Up to 60 days post-treatment
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study.
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
Measured: Up to Day 70 of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2012 (estimated)
- Study start10 Oct 2012
- Primary completion18 Mar 2015
- Study completion16 Apr 2015
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-Associated Diarrhea (CDAD)Studies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 611 participants (actual)
Sponsor and investigators
- Lead sponsor
- Optimer Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01691248
- Sponsor's protocol ID
- 5119-001
- Other IDs
- OPT-80-302
- Acronym
- DEFLECT-1
- Status last verified
- Aug 2018
- First submitted
- 19 Sep 2012
- Last updated
- 18 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
de Almeida C, Wong M, Kleijn HJ, Wrishko RE. Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant. Clin Ther. 2023 Apr;45(4):356-362. doi: 10.1016/j.clinthera.2023.02.006. Epub 2023 Mar 9.
PubMed 36906440Mullane KM, Winston DJ, Nooka A, Morris MI, Stiff P, Dugan MJ, Holland H, Gregg K, Adachi JA, Pergam SA, Alexander BD, Dubberke ER, Broyde N, Gorbach SL, Sears PS. A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2019 Jan 7;68(2):196-203. doi: 10.1093/cid/ciy484.
PubMed 29893798
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DEFLECT-1: A Phase 3b Multi-Center, Double-Blind, Randomized, Placebo Controlled Study to Demonstrate the Safety and Efficacy of Fidaxomicin for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01691248
- Acronym / sponsor ID
- DEFLECT-1 / 5119-001
- Keywords
- Clostridium difficile, Clostridium difficile-Associated Diarrhea, Prophylaxis, Hematopoietic Stem Cell Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 611 participants (actual)
- Lead sponsor
- Optimer Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 10 Oct 2012 (actual)
- Primary completion
- 18 Mar 2015 (actual)
- Study completion
- 16 Apr 2015 (actual)
- First posted
- 24 Sep 2012 (estimated)
- Results
- Posted 12 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to demonstrate the efficacy and safety of Fidaxomicin versus placebo for prophylaxis against Clostridium difficile-Associated Diarrhea (CDAD) in adult participants undergoing hematopoietic stem cell transplantation (HSCT). The primary hypothesis is that Fidaxomicin is superior to placebo in preventing CDAD in participants undergoing HSCT.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fidaxomicin | Active comparator | Drug: fidaxomicin200 mg Fidaxomicin tablet once daily for no longer than 40 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet once daily for no longer than 40 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female 18 years of age or older.
- Females of childbearing potential must be using an adequate and reliable method of contraception (e.g., abstinence, barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Males and females must agree to avoid conception during treatment and for four weeks following the end of study treatment.
- Is undergoing HSCT with planned Fluoroquinolone prophylaxis.
- Informed consent is provided.
Key exclusion criteria (8 listed)
- Ongoing active CDAD infection (as evidenced by clinical signs of diarrhea along with the presence of either toxin A and/or B [or their respective genes, tcdA and/or tcdB] of C. difficile in the stool) or current treatment for CDAD.
- Undergoing cord blood transplants.
- Has fulminant colitis, toxic megacolon, or ileus.
- A history of inflammatory bowel disease (ulcerative colitis or Crohn's disease).
- Women who are pregnant or are actively breast feeding (all women of childbearing potential must have a negative pregnancy test result prior to dosing study drug).
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 |
|---|---|---|
| fidaxomicinAlso: DIFICID, DIFICLIR, OPT-80, PAR-101Fidaxomicin 200 mg tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Study drug treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Study drug treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days. | Drug | Fidaxomicin |
| PlaceboPlacebo tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days. | Drug | Placebo |
Primary outcome
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.
Time frame: Up to 30 days post-treatment
CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
2 secondary outcomes
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment.
Time frame: Up to 60 days post-treatment
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study.
Time frame: Up to Day 70 of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36906440de Almeida C, Wong M, Kleijn HJ, Wrishko RE. Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant. Clin Ther. 2023 Apr;45(4):356-362. doi: 10.1016/j.clinthera.2023.02.006. Epub 2023 Mar 9.
- Derived from this study: PubMed 29893798Mullane KM, Winston DJ, Nooka A, Morris MI, Stiff P, Dugan MJ, Holland H, Gregg K, Adachi JA, Pergam SA, Alexander BD, Dubberke ER, Broyde N, Gorbach SL, Sears PS. A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2019 Jan 7;68(2):196-203. doi: 10.1093/cid/ciy484.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Related trials for Clostridium Difficile-Associated Diarrhea (CDAD)
Recruiting
Advantages and Disadvantages of TOXCLEAN As Add on Treatment to SOC in Patients with Clostridium Difficile-associated Diarrhea
Clostridium; Difficile, As Cause of Disease Classified Elsewhere, Clostridium Difficile Diarrhea
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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fidaxomicin in people with Clostridium Difficile-Associated Diarrhea (CDAD), run by Optimer Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
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 4 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 18 Sep 2018. 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. Some participants in this study may receive a placebo. 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 12 Apr 2016). 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?
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up. (time frame: Up to 30 days post-treatment). 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 NCT01691248, 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 18 Sep 2018.