Crohn DiseasePhase 2PAZAZNCT04186247

Personalized AZithromycin/metronidAZole Therapy in Pediatric Crohn's Disease (CD)

A Phase 2 study testing Azithromycin and Metronidazole in people with Crohn Disease and Pediatric Crohns Disease, run by University of North Carolina, Chapel Hill at 5 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 3 to 17 years
Conditions the study is for: Crohn Disease, Pediatric Crohns Disease
What is being tested?: Azithromycin and Metronidazole
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 5 sitesin 4 countries
Study dates: 13 Aug 2021to 31 Dec 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Provision of signed and dated informed consent form (and assent form, as applicable);
Stated willingness to comply with all study procedures and availability for the duration of the study;
Male or female, aged 3 to 17 years;
Diagnosed with CD according to standard clinical and histological criteria, within 36 months of week 0;
Exhibiting mild to moderate symptoms of active disease, as determined by a Pediatric Crohn's Disease Activity Index (PCDAI) score >10 (or > 7.5 excluding the height item) and ≤37.5;
Fecal calprotectin level >=250 µg/g within 30 days prior to week 0 visit based on local measurement, if available, or to be arranged with lead site if an endoscopy is not performed within 30 days prior to week 0 visit.

Who cannot join

Current or previous use of biologic therapy;
Presence of stricturing, penetrating (intestinal or perianal) and/or fistulizing CD;
Pregnancy or lactation;
Have undergone intestinal resection;
Positive Clostridium Difficile toxin;
Treatment with another investigational drug or other intervention within 30 days before week 0;

Show all 21Show fewer

Risk factors for arrhythmia including history of prolonged corrected QT interval (QTc), hypokalemia or hypomagnesemia, resting bradycardia, or concurrent treatment with other drugs with potential for QT prolongation;
History of cockayne syndrome;
Prior diagnosis of any hematologic condition/blood dyscrasia which may result in leukopenia (even if leukocyte count is normal at screening);
Known allergy or intolerance to azithromycin or metronidazole;
Subjects who received intravenous anti-infective within 35 days prior to week 0 visit or anti-infectives within 14 days prior to the week 0 visit;
Subject on oral aminosalicylates who has not been on stable doses for greater than, or discontinued within, at least 14 days prior to week 0;
Subject on cyclosporine, tacrolimus or mycophenolate mofetil. Stable doses (no change within 14 days prior to week 0) of azathioprine, 6-mercaptopurine or methotrexate (MTX) are not a reason for exclusion;
Subject who received fecal microbial transplantation within 35 days prior to week 0 visit;
Screening laboratory and other analyses show any of the following abnormal results:
aspartate transaminase (AST), alanine transaminase (ALT) > 2 X upper limit of the reference range,
White blood cell (WBC) count < 3.0 X 109/L,
Total bilirubin >= 20 micromol/liter (1.17 mg/dL); except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome,
Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula of < 30 mL/min/1.73 m²,
Hemoglobin < 80 gram/liter,
Platelets < 100,000/µL.

Trial locations and contacts

5 sites in 4 countries.

Country

City, postcode or hospital

5 sites in 4 countries

United States2 sites

University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
UCSF Benioff Children's Hospital
San Francisco, California, 94158

Other trials in United States

Canada1 site

IWK Health Centre
Halifax

Other trials in Canada

Israel1 site

Wolfson Medical Centre
Tel Aviv

Other trials in Israel

Netherlands1 site

Amsterdam UMC
Amsterdam

Other trials in Netherlands

About this study

Official title: Personalized AZithromycin/metronidAZole, in Combination With Standard Induction Therapy, to Achieve a Fecal Microbiome Community Structure and Metagenome Changes Associated With Sustained Remission in Pediatric Crohn's Disease (CD): a Pilot Study

Read the detailed description

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).

Conditions: Crohn Disease, Pediatric Crohns Disease
Being tested: Azithromycin, Metronidazole, Standard of Care
Keywords: Microbiome
Medical subject headings: Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AzithromycinDrug
Also called Zithromax, Zmax
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
MetronidazoleDrug
Also called Flagyl
Weeks 4-12: 20 mg/kg/day of metronidazole (10 mg/kg twice daily to a maximum of 1000 mg/day) for 8 weeks
Standard of CareOther
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.

Study groups in NCT04186247
Study group	Role	What they receive
Standard of Care	Other	SOC induction (nutritional therapy) for up to 12 weeks, as assigned by the treating gastroenterologist prior to study entry. Receives: Other: Standard of Care
Standard of Care + Antibiotics	Experimental	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) Receives: Drug: Azithromycin; Drug: Metronidazole; Other: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Week 52
Feasibility of Multinational Microbiome-randomized Trial
The number of participants with microbiome data available at Week 4/5.
Measured: Week 4/5

Secondary outcomes (4)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Aug 202131 Dec 2023

First posted4 Dec 2019
Study start13 Aug 2021
Primary completion31 Dec 2023
Study completion31 Dec 2023

Why it stopped: The DSMB concluded that feasibility endpoints were reached in time for Week 4 but no participants receiving standard of care dietary treatment could be randomized based on the at-risk of the microbiome signature.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Crohn DiseaseStudies of the same condition, open and under way.
More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04186247
Sponsor's protocol ID: 19-3100
Other IDs: 585718
Acronym: PAZAZ
Status last verified: Aug 2024
First submitted: 2 Dec 2019
Last updated: 29 Jun 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: 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.

Publications

Verburgt CM, Dunn KA, Otley A, Heyman MB, Verstraete S, Sunseri W, Sylvester F, de Meij T, Comeau A, Langille M, de Jonge WJ, Benninga MA, Van Limbergen JE. Personalised azithromycin+metronidazole (PAZAZ), in combination with standard induction therapy, to achieve a faecal microbiome community structure and metagenome changes associated with sustained remission in paediatric Crohn's disease (CD): protocol of a pilot study. BMJ Open. 2023 Feb 1;13(2):e064944. doi: 10.1136/bmjopen-2022-064944.
PubMed 36725090

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Crohn Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Personalized AZithromycin/metronidAZole, in Combination With Standard Induction Therapy, to Achieve a Fecal Microbiome Community Structure and Metagenome Changes Associated With Sustained Remission in Pediatric Crohn's Disease (CD): a Pilot Study
ClinicalTrials.gov ID: NCT04186247
Acronym / sponsor ID: PAZAZ / 19-3100
Conditions: Crohn Disease, Pediatric Crohns Disease
Keywords: Microbiome
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The DSMB concluded that feasibility endpoints were reached in time for Week 4 but no participants receiving standard of care dietary treatment could be randomized based on the at-risk of the microbiome signature.
Enrolment: 13 participants (actual)
Lead sponsor: University of North Carolina, Chapel HillUniversity, hospital or other
Collaborators: Crohn's and Colitis Foundation, University of Amsterdam, OM Pharma SA
Study start: 13 Aug 2021 (actual)
Primary completion: 31 Dec 2023 (actual)
Study completion: 31 Dec 2023 (actual)
First posted: 4 Dec 2019 (actual)
Results: Posted 29 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Standard of Care	Other	Other: Standard of CareSOC induction (nutritional therapy) for up to 12 weeks, as assigned by the treating gastroenterologist prior to study entry.
Standard of Care + Antibiotics	Experimental	Drug: Azithromycin, Drug: Metronidazole, Other: Standard of CareSOC 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)

Who may qualify

Ages: 3 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

Provision of signed and dated informed consent form (and assent form, as applicable);
Stated willingness to comply with all study procedures and availability for the duration of the study;
Male or female, aged 3 to 17 years;
Diagnosed with CD according to standard clinical and histological criteria, within 36 months of week 0;
Exhibiting mild to moderate symptoms of active disease, as determined by a Pediatric Crohn's Disease Activity Index (PCDAI) score >10 (or > 7.5 excluding the height item) and ≤37.5;

Key exclusion criteria (21 listed)

Current or previous use of biologic therapy;
Presence of stricturing, penetrating (intestinal or perianal) and/or fistulizing CD;
Pregnancy or lactation;
Have undergone intestinal resection;
Positive Clostridium Difficile toxin;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AzithromycinAlso: Zithromax, ZmaxWeeks 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	Drug	Standard of Care + Antibiotics
MetronidazoleAlso: FlagylWeeks 4-12: 20 mg/kg/day of metronidazole (10 mg/kg twice daily to a maximum of 1000 mg/day) for 8 weeks	Drug	Standard of Care + Antibiotics
Standard of CareSOC 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.	Other	Standard of Care, Standard of Care + Antibiotics

Primary outcome

Number of Participants With Sustained Remission
Time frame: Week 52
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.
Feasibility of Multinational Microbiome-randomized Trial
Time frame: Week 4/5
The number of participants with microbiome data available at Week 4/5.

4 secondary outcomes

Number of Participants With Normal Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52
Time frame: Week 52
Number of Participants With Normal Fecal Calprotectin Levels in Stool at Week 52
Time frame: Week 52
Number of Participants With Normal C-Reactive Protein (CRP) Levels in Blood at Week 52
Time frame: Week 52
IMPACT-III Score at Week 52
Time frame: Week 52

Results and safety

Results posted to the registry on 29 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Standard of Care	13	11
High Risk for Relapse (Group A1)	0	0
High Risk for Relapse Standard of Care + Antibiotics (Group A2)	0	0
Normal Risk for Relapse Standard of Care (Group B)	0	0
No Remission Independent of Microbiome + Antibiotics	0	0

Primary outcome: Number of Participants With Sustained Remission

Time frame: Week 52. Count of participants. Unit: Participants

Measure	Standard of Care n = 2	Standard of Care + Antibiotics n = 1
Value	2	1

Population analysed: No children carrying an at-risk microbiome achieved remission by Week 4; therefore, no participants were eligible for randomization and thus these data were not collected. Only participants who remained in the study until Week 52 are reported. The other participants either refused to continue dietary therapy or needed additional medical therapy in the course of the 52 weeks due to disease activity.

Primary outcome: Feasibility of Multinational Microbiome-randomized Trial

Time frame: Week 4/5. Count of participants. Unit: Participants

Measure	Standard of Care n = 2	High Risk for Relapse (Group A1) n = 0	High Risk for Relapse Standard of Care + Antibiotics (Group A2) n = 0	Normal Risk for Relapse Standard of Care (Group B) n = 8	No Remission Independent of Microbiome + Antibiotics n = 3
Value	2	–	–	8	3

Population analysed: Two participants provided microbiome data at Baseline but did not continue after Week 1. No participants were randomized into Group A1 or Group A2. Eight participants continued SOC in Group B and three participants were eligible for antibiotics based on microbiome data and not achieving remission in Group C (two participants received antibiotics).

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the time of signing informed consent until study conclusion (up to 52 weeks).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High Risk for Relapse (Group A1)	0 of 1 (0%)	0 of 1 (0%)	0 of 1
High Risk for Relapse Standard of Care + Antibiotics (Group A2)	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Normal Risk for Relapse Standard of Care (Group B)	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
No Remission Independent of Microbiome + Antibiotics (Group C)	0 of 1 (0%)	1 of 1 (100%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36725090Verburgt CM, Dunn KA, Otley A, Heyman MB, Verstraete S, Sunseri W, Sylvester F, de Meij T, Comeau A, Langille M, de Jonge WJ, Benninga MA, Van Limbergen JE. Personalised azithromycin+metronidazole (PAZAZ), in combination with standard induction therapy, to achieve a faecal microbiome community structure and metagenome changes associated with sustained remission in paediatric Crohn's disease (CD): protocol of a pilot study. BMJ Open. 2023 Feb 1;13(2):e064944. doi: 10.1136/bmjopen-2022-064944.
Individual participant dataSharing planned: 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.

Related trials for Crohn Disease

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Johan E Van Limbergen, MD, PhD principal investigator

Amsterdam UMC

Arie Levine, MD study chair

Edith Wolfson Medical Centre, Tel Aviv

Francisco Sylvester, MD study chair

University North Carolina

5 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azithromycin and Metronidazole in people with Crohn Disease and Pediatric Crohns Disease, run by University of North Carolina, Chapel Hill at 5 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Canada, Israel, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Sustained Remission (time frame: Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04186247, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2025.