search
Back to results

Oral Vancomycin vs Placebo in the Prevention of Recurrence of Clostridioides Difficile's Infection (PREVAN)

Primary Purpose

Clostridioides Difficile Infection

Status
Recruiting
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Oral Vancomycin
Placebo
Sponsored by
Julia Orígüen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Clostridioides Difficile Infection focused on measuring Vancomycin oral capsules

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age equal or superior to 18 years
  • Previous history of Clostridioides difficile infection in the 90 days before the study enrolment
  • Need for hospitalization and need of antibiotic therapy
  • Signature of informed consent

Exclusion Criteria:

  • Woman of childbearing age, pregnant woman, or breastfeeding woman
  • Patients allergic to vancomycin
  • Impossibility of fulfilling the study protocol
  • Critically ill condition or life expectancy less than 30 days
  • Patients with diagnosed inflammatory bowel disease or with any conditions that produce chronic diarrhea
  • Patients that meet diarrhea criteria or that present a Clostridioides Difficile infection at the time of patient's recruitment or during the 3 days prior.
  • Antibiotic therapy with oral vancomycin at the time of patient's selection or during the 3 days prior, or with any drug that is effective against Clostrioides Difficile.
  • Antibiotic prophylaxis with oral vancomycin or with any drug that is effective against Clostrioides difficile during the 90 days before the recruitment.
  • Systemic antibiotic therapy for 72 hours or more before the recruitment
  • Enrolment in another clinical trial that evaluates other drugs' effectiveness
  • Estimated use of systemic antibiotic therapy for more than 4 weeks

Sites / Locations

  • Rafael San JuanRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention group

Placebo group

Arm Description

A group of patients will be treated with a blinded capsule that contains 125mg of vancomycin every 6 hours for 10 days.

A group of patients will be treated with a blinded capsule that contains a placebo every 6 hours for 10 days.

Outcomes

Primary Outcome Measures

Effectiveness of treatment with oral vancomycin in the prevention of Clostridioides difficile
Absolute difference in the rate of C. difficile infection recurrences with vancomycin Vs placebo.

Secondary Outcome Measures

Effectiveness of treatment with oral vancomycin according to the number of previous recurrences
The absolute difference in the rate of C. difficile infection recurrences with vancomycin vs placebo stratified by index CDI episode (first episode or recurrence)
Effectiveness of treatment with oral vancomycin in diminishing the severity of the recurrence
The absolute difference in the rate of severe C. difficile infection recurrences with vancomycin vs placebo
Effectiveness of treatment with oral vancomycin depending on antibiotic therapy
The absolute difference in the rate of C. difficile infection recurrences with vancomycin vs placebo stratified by the type of systemic antibiotic therapy prescribed.
Tolerance and safety of treatment with oral vancomycin
Rate of major adverse events and drug-related adverse events.

Full Information

First Posted
March 22, 2022
Last Updated
April 20, 2023
Sponsor
Julia Orígüen
Collaborators
Instituto de Salud Carlos III
search

1. Study Identification

Unique Protocol Identification Number
NCT05320068
Brief Title
Oral Vancomycin vs Placebo in the Prevention of Recurrence of Clostridioides Difficile's Infection
Acronym
PREVAN
Official Title
Phase III,Randomized,Double-blinded Clinical Trial to Evaluate the Effectiveness and Safety of Oral Vancomycin Vs Placebo in the Prevention of Recurrence of C.Difficile Infection in Patients Under Treatment With Systemic Antibiotic Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 2, 2022 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Julia Orígüen
Collaborators
Instituto de Salud Carlos III

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A phase III randomized clinical trial in proportion 2:1 in favor of oral vancomycin (experimental treatment), multicentric, national, double-blinded, controlled with placebo. The main objective is to evaluate the effectiveness of treatment with oral vancomycin to reduce the incidence of Clostridioides difficile infection (CDI) in patients who suffered previous CDI and who need further hospitalization and treatment with systemic antibiotic therapy in the 90 days after the first CDI.
Detailed Description
As secondary objectives the investigators intend to: Evaluate the effectiveness of the treatment with oral vancomycin as part of the prophylaxis arsenal to prevent ICD in patients with previous ICD episodes stratified by the number of previous recurrences. Compare the severity of recurrences in both study groups. Compare the effectiveness of the treatment with oral vancomycin depending on the type of systemic antibiotic therapy prescribed. Evaluate the tolerance and the safety of the treatment with oral vancomycin in terms of secondary effects and difficulty in therapeutic compliance. Evaluate if the treatment with oral vancomycin has an effect in diminishing the severity of ICD recurrences.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridioides Difficile Infection
Keywords
Vancomycin oral capsules

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Proportion 2:1 in favour to the intervention arm
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
108 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
A group of patients will be treated with a blinded capsule that contains 125mg of vancomycin every 6 hours for 10 days.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
A group of patients will be treated with a blinded capsule that contains a placebo every 6 hours for 10 days.
Intervention Type
Drug
Intervention Name(s)
Oral Vancomycin
Intervention Description
A blinded capsule that contains 125mg of vancomycin every 6 hours during 10 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A blinded capsule that contains no vancomycin every 6 hours during 10 days.
Primary Outcome Measure Information:
Title
Effectiveness of treatment with oral vancomycin in the prevention of Clostridioides difficile
Description
Absolute difference in the rate of C. difficile infection recurrences with vancomycin Vs placebo.
Time Frame
60 days after the beginning of the intervention
Secondary Outcome Measure Information:
Title
Effectiveness of treatment with oral vancomycin according to the number of previous recurrences
Description
The absolute difference in the rate of C. difficile infection recurrences with vancomycin vs placebo stratified by index CDI episode (first episode or recurrence)
Time Frame
60 days after the beginning of the intervention
Title
Effectiveness of treatment with oral vancomycin in diminishing the severity of the recurrence
Description
The absolute difference in the rate of severe C. difficile infection recurrences with vancomycin vs placebo
Time Frame
60 days after the beginning of the intervention
Title
Effectiveness of treatment with oral vancomycin depending on antibiotic therapy
Description
The absolute difference in the rate of C. difficile infection recurrences with vancomycin vs placebo stratified by the type of systemic antibiotic therapy prescribed.
Time Frame
60 days after the beginning of the intervention
Title
Tolerance and safety of treatment with oral vancomycin
Description
Rate of major adverse events and drug-related adverse events.
Time Frame
60 days after the beginning of the intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age equal or superior to 18 years Previous history of Clostridioides difficile infection in the 90 days before the study enrolment Need for hospitalization and need of antibiotic therapy Signature of informed consent Exclusion Criteria: Woman of childbearing age, pregnant woman, or breastfeeding woman Hypersensitivity to vancomycin Inability to comply with study protocol Critically ill condition or life expectancy less than 30 days Patients with diagnosed inflammatory bowel disease or with any conditions that produce chronic diarrhea Fulfilment of the criteria for diarrhea or diagnosis of CDI at the time of assessment for eligibility or in the previous 3 days Therapy with oral vancomycin or any other agent with activity against C. difficile for >48 hours in the previous 3 days;. Prophylaxis with oral vancomycin or any other agent with activity against C. difficile within the 70 days before the assessment for eligibility Systemic antibiotic therapy for 72 hours or more before the recruitment Ongoing enrolment in another RCT evaluating the effectiveness of other drugs Estimated use of systemic antibiotic therapy for more than 4 weeks
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
RAFAEL SAN-JUAN, M.D
Phone
0034609488076
Email
rafael.san@salud.madrid.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
RAFAEL SAN-JUAN
Organizational Affiliation
HOSPITAL 12 DE OCTUBRE
Official's Role
Study Chair
Facility Information:
Facility Name
Rafael San Juan
City
Madrid
ZIP/Postal Code
28032
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
RAFAEL SAN-JUAN, MD.PhD.
Phone
609488076
Ext
4843
Email
rafasjg@yahoo.es
First Name & Middle Initial & Last Name & Degree
José María Aguado, MD. PhD.
Phone
0034913908000
Ext
4632
Email
jaguadog1@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie results in a publication will be shared
IPD Sharing Time Frame
Data generated by the research will be made available as soon as possible, wherever legally and ethically possible. It is Planned to share data starting 9 months after publication, and data will be available for 24 months thereafter.
IPD Sharing Access Criteria
IPD will be shared with investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Proposals should be directed to rafael.san@salud.madrid.org. To gain access, data requestors will need to sign a data access agreement.
Citations:
PubMed Identifier
24670166
Citation
Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin SK; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014 Mar 27;370(13):1198-208. doi: 10.1056/NEJMoa1306801. Erratum In: N Engl J Med. 2022 Jun 16;386(24):2348.
Results Reference
background
PubMed Identifier
31976779
Citation
Rauseo AM, Olsen MA, Reske KA, Dubberke ER. Strategies to prevent adverse outcomes following Clostridioides difficile infection in the elderly. Expert Rev Anti Infect Ther. 2020 Mar;18(3):203-217. doi: 10.1080/14787210.2020.1717950. Epub 2020 Jan 27.
Results Reference
background
PubMed Identifier
22136747
Citation
Asensio A, Monge D. [Epidemiology of Clostridium difficile infection in Spain]. Enferm Infecc Microbiol Clin. 2012 Jun;30(6):333-7. doi: 10.1016/j.eimc.2011.09.010. Epub 2011 Dec 2. Spanish.
Results Reference
background
PubMed Identifier
18761902
Citation
Asensio A, Vaque-Rafart J, Calbo-Torrecillas F, Gestal-Otero JJ, Lopez-Fernandez F, Trilla-Garcia A, Canton R; EPINE Working Group. Increasing rates in Clostridium difficile infection (CDI) among hospitalised patients, Spain 1999-2007. Euro Surveill. 2008 Jul 31;13(31):18943.
Results Reference
background
PubMed Identifier
16704777
Citation
McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006 Mar;12(3):409-15. doi: 10.3201/eid1205.051064.
Results Reference
background
PubMed Identifier
22752869
Citation
Eyre DW, Walker AS, Wyllie D, Dingle KE, Griffiths D, Finney J, O'Connor L, Vaughan A, Crook DW, Wilcox MH, Peto TE; Infections in Oxfordshire Research Database. Predictors of first recurrence of Clostridium difficile infection: implications for initial management. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S77-87. doi: 10.1093/cid/cis356.
Results Reference
background
PubMed Identifier
23447638
Citation
Rodriguez-Pardo D, Almirante B, Bartolome RM, Pomar V, Mirelis B, Navarro F, Soriano A, Sorli L, Martinez-Montauti J, Molins MT, Lung M, Vila J, Pahissa A; Barcelona Clostridium difficile Study Group. Epidemiology of Clostridium difficile infection and risk factors for unfavorable clinical outcomes: results of a hospital-based study in Barcelona, Spain. J Clin Microbiol. 2013 May;51(5):1465-73. doi: 10.1128/JCM.03352-12. Epub 2013 Feb 27.
Results Reference
background
PubMed Identifier
23121551
Citation
Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012 Dec;18 Suppl 6:21-7. doi: 10.1111/1469-0691.12046.
Results Reference
background
PubMed Identifier
19941990
Citation
Leav BA, Blair B, Leney M, Knauber M, Reilly C, Lowy I, Gerding DN, Kelly CP, Katchar K, Baxter R, Ambrosino D, Molrine D. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010 Jan 22;28(4):965-9. doi: 10.1016/j.vaccine.2009.10.144. Epub 2009 Nov 24.
Results Reference
background
PubMed Identifier
15889355
Citation
Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Fulop K, Godin D, Bourassa C. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005 Jun 1;40(11):1591-7. doi: 10.1086/430315. Epub 2005 Apr 25.
Results Reference
background
PubMed Identifier
19162027
Citation
Hu MY, Katchar K, Kyne L, Maroo S, Tummala S, Dreisbach V, Xu H, Leffler DA, Kelly CP. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology. 2009 Apr;136(4):1206-14. doi: 10.1053/j.gastro.2008.12.038. Epub 2008 Dec 13.
Results Reference
background
PubMed Identifier
25626326
Citation
Deshpande A, Pasupuleti V, Thota P, Pant C, Rolston DD, Hernandez AV, Donskey CJ, Fraser TG. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015 Apr;36(4):452-60. doi: 10.1017/ice.2014.88. Epub 2015 Jan 28.
Results Reference
background
PubMed Identifier
20224312
Citation
Cadena J, Thompson GR 3rd, Patterson JE, Nakashima B, Owens A, Echevarria K, Mortensen EM. Clinical predictors and risk factors for relapsing Clostridium difficile infection. Am J Med Sci. 2010 Apr;339(4):350-5. doi: 10.1097/MAJ.0b013e3181d3cdaa.
Results Reference
background
PubMed Identifier
20153547
Citation
Ghantoji SS, Sail K, Lairson DR, DuPont HL, Garey KW. Economic healthcare costs of Clostridium difficile infection: a systematic review. J Hosp Infect. 2010 Apr;74(4):309-18. doi: 10.1016/j.jhin.2009.10.016. Epub 2010 Feb 12.
Results Reference
background
PubMed Identifier
26753991
Citation
Larrainzar-Coghen T, Rodriguez-Pardo D, Puig-Asensio M, Rodriguez V, Ferrer C, Bartolome R, Pigrau C, Fernandez-Hidalgo N, Pumarola T, Almirante B. First recurrence of Clostridium difficile infection: clinical relevance, risk factors, and prognosis. Eur J Clin Microbiol Infect Dis. 2016 Mar;35(3):371-8. doi: 10.1007/s10096-015-2549-9. Epub 2016 Jan 11.
Results Reference
background
PubMed Identifier
27806252
Citation
Carpenter BP, Hennessey EK, Bryant AM, Khoury JA, Crannage AJ. Identification of Factors Impacting Recurrent Clostridium difficile Infection and Development of a Risk Evaluation Tool. J Pharm Pharm Sci. 2016 Jul-Sep;19(3):349-356. doi: 10.18433/J32S41.
Results Reference
background
PubMed Identifier
24898123
Citation
Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization among hospitalized patients with an initial CDI episode: a retrospective cohort study. BMC Infect Dis. 2014 Jun 4;14:306. doi: 10.1186/1471-2334-14-306.
Results Reference
background
PubMed Identifier
30307842
Citation
Aldape MJ, Rice SN, Field KP, Bryant AE, Stevens DL. Sub-lethal doses of surotomycin and vancomycin have similar effects on Clostridium difficile virulence factor production in vitro. J Med Microbiol. 2018 Dec;67(12):1689-1697. doi: 10.1099/jmm.0.000852. Epub 2018 Oct 11.
Results Reference
background
PubMed Identifier
27318333
Citation
Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016 Sep 1;63(5):651-3. doi: 10.1093/cid/ciw401. Epub 2016 Jun 17.
Results Reference
background
PubMed Identifier
27567123
Citation
Cheng MP, Parkes LO, Lee TC. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016 Nov 15;63(10):1391-1392. doi: 10.1093/cid/ciw595. Epub 2016 Aug 27. No abstract available.
Results Reference
background
PubMed Identifier
27619835
Citation
Carignan A, Poulin S, Martin P, Labbe AC, Valiquette L, Al-Bachari H, Montpetit LP, Pepin J. Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections. Am J Gastroenterol. 2016 Dec;111(12):1834-1840. doi: 10.1038/ajg.2016.417. Epub 2016 Sep 13.
Results Reference
background
PubMed Identifier
31560051
Citation
Johnson SW, Brown SV, Priest DH. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Clin Infect Dis. 2020 Aug 22;71(5):1133-1139. doi: 10.1093/cid/ciz966.
Results Reference
background
PubMed Identifier
19929973
Citation
Bauer MP, Kuijper EJ, van Dissel JT; European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009 Dec;15(12):1067-79. doi: 10.1111/j.1469-0691.2009.03099.x.
Results Reference
background
PubMed Identifier
29462280
Citation
McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085.
Results Reference
background
PubMed Identifier
29309934
Citation
Ooijevaar RE, van Beurden YH, Terveer EM, Goorhuis A, Bauer MP, Keller JJ, Mulder CJJ, Kuijper EJ. Update of treatment algorithms for Clostridium difficile infection. Clin Microbiol Infect. 2018 May;24(5):452-462. doi: 10.1016/j.cmi.2017.12.022. Epub 2018 Jan 6.
Results Reference
background
PubMed Identifier
22321770
Citation
Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K, Sears P, Gorbach S; OPT-80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012 Apr;12(4):281-9. doi: 10.1016/S1473-3099(11)70374-7. Epub 2012 Feb 8.
Results Reference
background
PubMed Identifier
24799326
Citation
Johnson S, Louie TJ, Gerding DN, Cornely OA, Chasan-Taber S, Fitts D, Gelone SP, Broom C, Davidson DM; Polymer Alternative for CDI Treatment (PACT) investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54. doi: 10.1093/cid/ciu313. Epub 2014 May 5.
Results Reference
background
PubMed Identifier
21288078
Citation
Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue YK; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011 Feb 3;364(5):422-31. doi: 10.1056/NEJMoa0910812.
Results Reference
background
PubMed Identifier
22752858
Citation
Weiss K, Allgren RL, Sellers S. Safety analysis of fidaxomicin in comparison with oral vancomycin for Clostridium difficile infections. Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S110-5. doi: 10.1093/cid/cis390.
Results Reference
background
PubMed Identifier
3110198
Citation
Charlson ME, Sax FL, MacKenzie CR, Braham RL, Fields SD, Douglas RG Jr. Morbidity during hospitalization: can we predict it? J Chronic Dis. 1987;40(7):705-12. doi: 10.1016/0021-9681(87)90107-x.
Results Reference
background

Learn more about this trial

Oral Vancomycin vs Placebo in the Prevention of Recurrence of Clostridioides Difficile's Infection

We'll reach out to this number within 24 hrs