Efficacy of Rifaximin in Preventing Campylobacteriosis

NCT02280044 | Completed Phase 2 Results DMC

• 1 other identifier: CIR296
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, double-blinded, placebo-controlled, in-patient trial evaluating the prophylactic efficacy of rifaximin against campylobacteriosis following challenge with C. jejuni.

Conditions

Dysentery; Diarrhea; Enteric Campylobacteriosis

Keywords

Campylobacter jejuni; rifaximin; antibiotic prophylaxis; dysentery; diarrhea

Outcome Measures

Primary Outcomes (1)

• Campylobacteriosis

  A clinical illness meeting at least one of the following patterns: * Moderate to severe diarrhea. * Fever (present on at least 2 occasions, at least 20 minutes apart) without diarrhea, plus an associated symptom (nausea, vomiting, abdominal cramps, tenesmus, or gross blood in ≥ 2 stools); with consideration of potential alternative diagnosis per clinical investigator based on illness time course and associated symptoms.

  120 hours after challenge

Study Arms (2)

rifaximin

EXPERIMENTAL

Subjects receiving rifaximin prophylaxis will be challenged with C. jejuni

Biological: Rifaximin intervention

placebo

PLACEBO COMPARATOR

Subjects receiving placebo will be challenged with C. jejuni

Biological: Placebo intervention

Interventions

Rifaximin intervention BIOLOGICAL

Rifaximin administered then Challenge with C jejuni

rifaximin

Placebo intervention BIOLOGICAL

Placebo administered then Challenge with C jejuni

placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between 18 and 50 years of age, inclusive
• General good health, without significant medical illness, abnormal physical examination findings or clinically significant laboratory abnormalities, as determined by the PI (may consult with the Research Monitor on a case-by-case basis)
• Demonstrate comprehension of the protocol procedures and knowledge of Campylobacter illness by passing a written examination (pass grade ≥ 70%)
• Willing to participate after informed consent obtained
• Available for all planned follow-up visits and remain available for clinic visits (for examination, blood draws and stool collection) and monitoring for 90 days post-challenge and by phone for 180 days post-challenge
• If the subject is female, she is eligible to enter if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses); or must have documentation of having undergone tubal ligation or hysterectomy. OR
• Childbearing potential; has a negative serum pregnancy test at screening and a negative urine pregnancy test on admission (Study Day -1), and agrees to the use of an efficacious hormonal or barrier method of birth control during the study, abstinence is acceptable

You may not qualify if:

• General health/issues
• Presence of a significant medical condition (e.g., psychiatric conditions; gastrointestinal disease, such as peptic ulcer,symptoms or evidence of active gastritis/dyspepsia, inflammatory bowel disease, irritable bowel syndrome (as defined by the Rome III criteria or medical diagnosis); alcohol or illicit drug abuse/dependency) or laboratory abnormalities which in the opinion of the investigator preclude participation in the study
• Evidence of Immunoglobulin A deficiency (serum IgA \< 7 mg/dL or below the limit of detection of assay)
• Positive serology results for HIV, HBsAg, or Hepatitis C virus antibodies
• Positive urine toxicology screen
• Significant abnormalities in screening laboratory hematology or serum chemistry, as determined by PI or PI in consultation with the Research Monitor and sponsor
• Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding receipt of the challenge inoculum or planned to be used during the active study period
• Nursing mother on the day of admittance to the inpatient unit

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Naval Medical Research Center: collaborator
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (1)

Center for Immunization Research, Johns Hopkins Bloomberg School of Public Heatlh

Baltimore, Maryland, 21205, United States

Location

Related Publications (13)

• Kirkpatrick BD, Lyon CE, Porter CK, Maue AC, Guerry P, Pierce KK, Carmolli MP, Riddle MS, Larsson CJ, Hawk D, Dill EA, Fingar A, Poly F, Fimlaid KA, Hoq F, Tribble DR. Lack of homologous protection against Campylobacter jejuni CG8421 in a human challenge model. Clin Infect Dis. 2013 Oct;57(8):1106-13. doi: 10.1093/cid/cit454. Epub 2013 Jul 9.

  PMID: 23840001 RESULT

• Riddle MS, Gutierrez RL, Verdu EF, Porter CK. The chronic gastrointestinal consequences associated with campylobacter. Curr Gastroenterol Rep. 2012 Oct;14(5):395-405. doi: 10.1007/s11894-012-0278-0.

  PMID: 22864805 RESULT

• Tribble DR, Baqar S, Scott DA, Oplinger ML, Trespalacios F, Rollins D, Walker RI, Clements JD, Walz S, Gibbs P, Burg EF 3rd, Moran AP, Applebee L, Bourgeois AL. Assessment of the duration of protection in Campylobacter jejuni experimental infection in humans. Infect Immun. 2010 Apr;78(4):1750-9. doi: 10.1128/IAI.01021-09. Epub 2010 Jan 19.

  PMID: 20086085 RESULT

• Tribble DR, Baqar S, Carmolli MP, Porter C, Pierce KK, Sadigh K, Guerry P, Larsson CJ, Rockabrand D, Ventone CH, Poly F, Lyon CE, Dakdouk S, Fingar A, Gilliland T, Daunais P, Jones E, Rymarchyk S, Huston C, Darsley M, Kirkpatrick BD. Campylobacter jejuni strain CG8421: a refined model for the study of Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects. Clin Infect Dis. 2009 Nov 15;49(10):1512-9. doi: 10.1086/644622.

  PMID: 19842970 RESULT

• Poly F, Read TD, Chen YH, Monteiro MA, Serichantalergs O, Pootong P, Bodhidatta L, Mason CJ, Rockabrand D, Baqar S, Porter CK, Tribble D, Darsley M, Guerry P. Characterization of two Campylobacter jejuni strains for use in volunteer experimental-infection studies. Infect Immun. 2008 Dec;76(12):5655-67. doi: 10.1128/IAI.00780-08. Epub 2008 Sep 22.

  PMID: 18809665 RESULT

• Flores J, Dupont HL, Jiang ZD, Okhuysen PC, Melendez-Romero JH, Gonzalez-Estrada A, Carrillo I, Paredes M. A randomized, double-blind, pilot study of rifaximin 550 mg versus placebo in the prevention of travelers' diarrhea in Mexico during the dry season. J Travel Med. 2011 Sep-Oct;18(5):333-6. doi: 10.1111/j.1708-8305.2011.00549.x. Epub 2011 Aug 1.

  PMID: 21896097 RESULT

• Martinez-Sandoval F, Ericsson CD, Jiang ZD, Okhuysen PC, Romero JH, Hernandez N, Forbes WP, Shaw A, Bortey E, DuPont HL. Prevention of travelers' diarrhea with rifaximin in US travelers to Mexico. J Travel Med. 2010 Mar-Apr;17(2):111-7. doi: 10.1111/j.1708-8305.2009.00385.x.

  PMID: 20412178 RESULT

• Steffen R, Sack DA, Riopel L, Jiang ZD, Sturchler M, Ericsson CD, Lowe B, Waiyaki P, White M, DuPont HL. Therapy of travelers' diarrhea with rifaximin on various continents. Am J Gastroenterol. 2003 May;98(5):1073-8. doi: 10.1111/j.1572-0241.2003.07283.x.

  PMID: 12809830 RESULT

• Infante RM, Ericsson CD, Jiang ZD, Ke S, Steffen R, Riopel L, Sack DA, DuPont HL. Enteroaggregative Escherichia coli diarrhea in travelers: response to rifaximin therapy. Clin Gastroenterol Hepatol. 2004 Feb;2(2):135-8. doi: 10.1016/s1542-3565(03)00322-7.

  PMID: 15017618 RESULT

• Armstrong AW, Ulukan S, Weiner M, Mostafa M, Shaheen H, Nakhla I, Tribble DR, Riddle MS. A randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rifaximin for the prevention of travelers' diarrhea in US military personnel deployed to Incirlik Air Base, Incirlik, Turkey. J Travel Med. 2010 Nov-Dec;17(6):392-4. doi: 10.1111/j.1708-8305.2010.00462.x.

  PMID: 21050319 RESULT

• Dupont HL, Jiang ZD, Belkind-Gerson J, Okhuysen PC, Ericsson CD, Ke S, Huang DB, Dupont MW, Adachi JA, De La Cabada FJ, Taylor DN, Jaini S, Martinez Sandoval F. Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol. 2007 Apr;5(4):451-6. doi: 10.1016/j.cgh.2007.02.004. Epub 2007 Mar 26.

  PMID: 17382603 RESULT

• DuPont HL, Jiang ZD, Ericsson CD, Adachi JA, Mathewson JJ, DuPont MW, Palazzini E, Riopel LM, Ashley D, Martinez-Sandoval F. Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis. 2001 Dec 1;33(11):1807-15. doi: 10.1086/323814. Epub 2001 Oct 23.

  PMID: 11692292 RESULT

• Rimmer JE, Harro C, Sack DA, Talaat KR, Gutierrez RL, DeNearing B, Brubaker J, Laird RM, Poly F, Maue AC, Jaep K, Alcala A, Mochalova Y, Gariepy CL, Chakraborty S, Guerry P, Tribble DR, Porter CK, Riddle MS. Rifaximin Fails to Prevent Campylobacteriosis in the Human Challenge Model: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis. 2018 Apr 17;66(9):1435-1441. doi: 10.1093/cid/cix1014.

  PMID: 29145631 DERIVED

MeSH Terms

Conditions

Dysentery; Diarrhea; Campylobacter Infections

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: David A Sack
• Organization: Johns Hopkins Bloomberg School of Public Health

dsack1@jhu.edu

443 287 8795

Study Officials

• Kawsar Talaat, M.D.

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: October 31, 2014
• Study Start: October 1, 2014
• Primary Completion: August 9, 2016
• Study Completion: August 9, 2016
• Last Updated: November 20, 2018
• Results First Posted: November 20, 2018

Record last verified: 2018-10

Locations

US (1)