A Phase 2 interventional study of Azithromycin and Metronidazole in Crohn Disease and Pediatric Crohns Disease, sponsored by University of North Carolina, Chapel Hill. Terminated at 5 sites in 4 countries. Open to participants aged 3 Years to 17 Years. Per ClinicalTrials.gov, last updated 2025-06-29.
Sponsored by University of North Carolina, Chapel Hill · Phase 2, Interventional, and Treatment
This is a multi-center, randomized, controlled open-label add-on design trial pilot study to evaluate the efficacy of personalized adjunctive antibiotic (azithromycin + metronidazole) therapy in pediatric subjects with mild to moderate Crohn's disease (CD) who have a microbiome profile associated with increased risk of early relapse. This an add-on design trial for subjects already receiving standard of care therapy to induce remission; there will be no placebos.
The study hypothesis is that adjunctive antibiotic therapy will improve clinical response to standard of care (SOC) induction therapy in a subgroup of CD patients with a relapse-associated microbiome profile.
Prior to starting SOC induction therapy at week 0, subjects will provide a baseline stool sample that will be screened for microbiome profiles associated with risk of relapse according to an established statistical model.
At week 4, subjects with a relapse-associated microbiome will be randomized into either a control arm that will continue to receive SOC induction therapy for an additional 8 weeks, or a treatment arm that will receive adjunctive antibiotic therapy in addition to continuing to receive SOC induction therapy for an additional 8 weeks. Subjects who do not have a relapse-associated microbiome will enter a separate control arm that will continue to receive SOC induction therapy and will have data collected for exploratory objectives. Subjects who are not in clinical remission by week 4 will receive antibiotic therapy regardless of microbiome signature at baseline. Subjects will be monitored for an additional 40 weeks after the treatment period (52 weeks total).
1,880 studies on the registry are indexed under Crohn Disease; 462 are open to participants now.
This study's enrollment of 13 is below the median of 66 across 1,188 interventional studies indexed under Crohn Disease.
Browse Crohn Disease studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.
Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Screening laboratory and other analyses show any of the following abnormal results:
SOC induction (nutritional therapy) for up to 12 weeks, as assigned by the treating gastroenterologist prior to study entry.
Other: Standard of Care
SOC induction (nutritional therapy) for up to 12 weeks, as assigned by the treating gastroenterologist prior to study entry. Azithromycin (weeks 4-12) Metronidazole (weeks 4-12)
Drug: Azithromycin · Drug: Metronidazole · Other: Standard of Care
Weeks 4-12: 7.5 mg/kg azithromycin once daily (500 mg/day maximum) for five consecutive days/ week for 4 weeks, and 3 times a week for the following 4 weeks
Also known as: Zithromax, Zmax
Weeks 4-12: 20 mg/kg/day of metronidazole (10 mg/kg twice daily to a maximum of 1000 mg/day) for 8 weeks
Also known as: Flagyl
SOC induction therapy is nutritional therapy (Crohn's disease exclusion diet + partial enteral nutrition) for up to 12 weeks. Induction therapy is as assigned by the treating gastroenterologist prior to study entry.
Number of Participants With Sustained Remission
Participants stratified based on carriage of an at-risk microbiome without need for re-induction for clinical flare (new course of nutritional therapy, need to restart steroids), steroid dependence, biologic (e.g. anti-TNF) use, and/or intestinal surgery.
Time frame: Week 52
Feasibility of Multinational Microbiome-randomized Trial
The number of participants with microbiome data available at Week 4/5.
Time frame: Week 4/5
Number of Participants With Normal Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, examination of abdomen, perirectal disease, and extraintestinal manifestations. Scores range from 0 to 100, with higher scores indicating greater disease activity.
Time frame: Week 52
Number of Participants With Normal Fecal Calprotectin Levels in Stool at Week 52
Fecal calprotectin is a non-invasive surrogate protein marker for bowel inflammation. The normal range is \<200 mcg/g.
Time frame: Week 52
Number of Participants With Normal C-Reactive Protein (CRP) Levels in Blood at Week 52
CRP is a blood protein marker of inflammation. CRP levels are classified as 'normal/low' or 'elevated/high' based on standard laboratory reference ranges.
Time frame: Week 52
IMPACT-III Score at Week 52
The IMPACT III questionnaire is a 35-item assessment of health-related quality of life in patients with inflammatory bowel disease (Crohn's disease \[CD\] or ulcerative colitis). In this study, participants aged 9 and older will complete this questionnaire at week 0, 12, 24, and 52. Participants mark an option from 1 to 5 for each item.The total scores range from 35 to 175, with higher scores representing a better quality of life.
Time frame: Week 52
Thirteen children were enrolled in the study to assess microbiome by Week 4. All participants received standard of care.
| Milestone | Standard of Care | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics |
|---|---|---|---|---|---|
| Started | 13 | 0 | 0 | 0 | 0 |
| Completed | 11 | 0 | 0 | 0 | 0 |
| Not completed | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 2 | 0 | 0 | 0 | 0 |
| Milestone | Standard of Care | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics |
|---|---|---|---|---|---|
| Started | 2 | 0 | 0 | 8 | 3 |
| Completed | 2 | 0 | 0 | 8 | 3 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
| Milestone | Standard of Care | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 8 | 3 |
| Completed | 0 | 0 | 0 | 2 | 1 |
| Not completed | 0 | 0 | 0 | 6 | 2 |
Participants stratified based on carriage of an at-risk microbiome without need for re-induction for clinical flare (new course of nutritional therapy, need to restart steroids), steroid dependence, biologic (e.g. anti-TNF) use, and/or intestinal surgery.
| Participants | Standard of Care | Standard of Care + Antibiotics |
|---|---|---|
| Number of Participants With Sustained Remission | 2 | 1 |
The number of participants with microbiome data available at Week 4/5.
| Participants | Standard of Care | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics |
|---|---|---|---|---|---|
| Feasibility of Multinational Microbiome-randomized Trial | 2 | — | — | 8 | 3 |
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, examination of abdomen, perirectal disease, and extraintestinal manifestations. Scores range from 0 to 100, with higher scores indicating greater disease activity.
| Participants | Standard of Care | Standard of Care + Antibiotics |
|---|---|---|
| Number of Participants With Normal Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52 | 2 | 1 |
Fecal calprotectin is a non-invasive surrogate protein marker for bowel inflammation. The normal range is \<200 mcg/g.
| Participants | Standard of Care | Standard of Care + Antibiotics |
|---|---|---|
| Number of Participants With Normal Fecal Calprotectin Levels in Stool at Week 52 | 1 | 1 |
CRP is a blood protein marker of inflammation. CRP levels are classified as 'normal/low' or 'elevated/high' based on standard laboratory reference ranges.
| Participants | Standard of Care | Standard of Care + Antibiotics |
|---|---|---|
| Number of Participants With Normal C-Reactive Protein (CRP) Levels in Blood at Week 52 | 2 | 1 |
The IMPACT III questionnaire is a 35-item assessment of health-related quality of life in patients with inflammatory bowel disease (Crohn's disease \[CD\] or ulcerative colitis). In this study, participants aged 9 and older will complete this questionnaire at week 0, 12, 24, and 52. Participants mark an option from 1 to 5 for each item.The total scores range from 35 to 175, with higher scores representing a better quality of life.
No measurements were reported for this outcome.
Collected over From the time of signing informed consent until study conclusion (up to 52 weeks).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| High Risk for Relapse (Group A1) | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| High Risk for Relapse Standard of Care + Antibiotics (Group A2) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Normal Risk for Relapse Standard of Care (Group B) | 0/9 (0%) | 0/9 (0%) | 2/9 (22.2%) |
| No Remission Independent of Microbiome + Antibiotics (Group C) | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Event | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics (Group C) |
|---|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 0/1 | 0/2 | 1/9 | 1/1 |
| HeadacheNervous system disorders | 0/1 | 0/2 | 0/9 | 1/1 |
| Change in tasteGastrointestinal disorders | 0/1 | 1/2 | 0/9 | 1/1 |
| DizzinessNervous system disorders | 0/1 | 1/2 | 0/9 | 1/1 |
| NauseaNervous system disorders | 0/1 | 0/2 | 1/9 | 0/1 |
| Elevated Liver EnzymesGastrointestinal disorders | 0/1 | 0/2 | 1/9 | 0/1 |
| Dilated Bile DuctGastrointestinal disorders | 0/1 | 0/2 | 1/9 | 0/1 |
| Limb PainMusculoskeletal and connective tissue disorders | 0/1 | 0/2 | 1/9 | 0/1 |
| Age, Categorical(Participants) | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics | Total |
|---|---|---|---|---|---|
| <=18 years | 1 | 2 | 9 | 1 | 13 |
| Between 18 and 65 years | 0 | 0 | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics | Total |
|---|---|---|---|---|---|
| Female | 0 | 0 | 6 | 1 | 7 |
| Male | 1 | 2 | 3 | 0 | 6 |
| Race and Ethnicity Not Collected(Participants) | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics | Total |
|---|---|---|---|---|---|
| Count of participants | — | — | — | — | 0 |
| Region of Enrollment(Participants) | High Risk for Relapse (Group A1) | High Risk for Relapse Standard of Care + Antibiotics (Group A2) | Normal Risk for Relapse Standard of Care (Group B) | No Remission Independent of Microbiome + Antibiotics | Total |
|---|---|---|---|---|---|
| Netherlands | 1 | 2 | 9 | 1 | 13 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with University of North Carolina.
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