Diarrhea, Dysentery, Enteric Campylobacteriosis
Conditions
Keywords
Campylobacter jejuni, rifaximin, antibiotic prophylaxis, dysentery, diarrhea
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.
Detailed description
30 healthy volunteers (2 of these were planned alternates) gave informed consent and were enrolled to participate in a study to determine the efficacy of prophylactic rifaximin in preventing diarrheal illness following challenge with C. jejuni, strain CG8421. Volunteers were screened for inclusion and exclusion criteria and were admitted to the inpatient unit of the Center for Immunization Research at Johns Hopkins University. Volunteers were treated with rifaximin or placebo in a double blind manner for four days, beginning the day prior to challenge. On the day of challenge, the volunteers were given 5x10(5) C. jejuni with bicarbonate buffer and were then monitored and treated for any symptoms. Stools were cultured daily for the excretion of C. jejuni and all subjects were treated with antibiotics to insure that the challenge strain has cleared prior to to discharge. Subjects were followed for six months following the inpatient phase to detect adverse events following the study.
Interventions
BIOLOGICALRifaximin intervention
Rifaximin administered then Challenge with C jejuni
BIOLOGICALPlacebo intervention
Placebo administered then Challenge with C jejuni
Sponsors
Naval Medical Research Center
Uniformed Services University of the Health Sciences
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female between 18 and 50 years of age, inclusive 2. 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) 3. Demonstrate comprehension of the protocol procedures and knowledge of Campylobacter illness by passing a written examination (pass grade ≥ 70%) 4. Willing to participate after informed consent obtained 5. 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 6. 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
Exclusion criteria
General health/issues 1. 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 2. Evidence of Immunoglobulin A deficiency (serum IgA \< 7 mg/dL or below the limit of detection of assay) 3. Positive serology results for HIV, HBsAg, or Hepatitis C virus antibodies 4. Positive urine toxicology screen 5. Significant abnormalities in screening laboratory hematology or serum chemistry, as determined by PI or PI in consultation with the Research Monitor and sponsor 6. 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 7. Nursing mother on the day of admittance to the inpatient unit Study-specific exclusionary conditions based on potential increased risk or complicating outcome ascertainment. (See protocol details for complete list of exclusions.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Campylobacteriosis | 120 hours after challenge | 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. |
Countries
United States
Participant flow
Pre-assignment details
Per protocol, a total of thirty subjects were admitted to the inpatient unit and randomized to receive investigational product on day -1 to ensure the target sample size was obtained. Two subjects received three doses of product but were discharged on Day 0 prior to challenge. Both subjects were randomized to the placebo arm.
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin Subjects receiving rifaximin prophylaxis will be challenged with C. jejuni | 15 |
| Placebo Subjects receiving placebo will be challenged with C. jejuni | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Planned alternate | 0 | 2 |
Baseline characteristics
| Characteristic | Rifaximin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 30 years | 31 years | 31 years |
| Race (NIH/OMB) Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Black or African American | 13 Participants | 27 Participants | 14 Participants |
| Race (NIH/OMB) Race More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race White | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 11 Participants | 21 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 |
| other Total, other adverse events | 13 / 15 | 13 / 13 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 120 hours after challenge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rifaximin | Campylobacteriosis | 13 Participants |
| Placebo | Campylobacteriosis | 11 Participants |
Post Hoc
Recrudescent Events
Recovered C jejuni from fecal specimen on follow-up after an apparent cure
Time frame: 84 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rifaximin | Recrudescent Events | 2 Participants |
| Placebo | Recrudescent Events | 3 Participants |