Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)

NCT ID: NCT01691248

Last Updated: 2018-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 611 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-10
• Study Completion Date: 2015-04-16

Brief 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). The primary hypothesis is that Fidaxomicin is superior to placebo in preventing CDAD in participants undergoing HSCT.

Conditions

Clostridium Difficile-Associated Diarrhea (CDAD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Fidaxomicin

200 mg Fidaxomicin tablet once daily for no longer than 40 days

Group Type: ACTIVE_COMPARATOR

fidaxomicin

Intervention Type: DRUG

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.

Placebo

Placebo tablet once daily for no longer than 40 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

fidaxomicin

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

DIFICID; DIFICLIR; OPT-80; PAR-101

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Optimer Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 36906440 (View on PubMed)

Mullane 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.

Reference Type: DERIVED

PMID: 29893798 (View on PubMed)

Other Identifiers

OPT-80-302

Identifier Type: OTHER

Identifier Source: secondary_id

5119-001

Identifier Type: -

Identifier Source: org_study_id