A Phase 2 interventional study of Azithromycin Pill and Placebo in Crohn's Disease Relapse and Biological Substance; Adverse Effect, sponsored by Rambam Health Care Campus. Recruiting at 9 sites in Israel. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-29.
Sponsored by Rambam Health Care Campus · Phase 2, Interventional, and Prevention
This is a randomized placebo-controlled trial in Crohn's disease patients before initiation of anti-tumor necrosis factor-α (anti-TNF) therapy that aims to test the effect of a pre-treatment short course of azithromycin therapy on immunogenicity
Anti-TNF agents are considered the mainstay of therapy for patients with inflammatory bowel diseases (IBD). Still, its efficacy is hampered by the development of anti-drug antibodies (ADA), which lead to non-responsiveness to this medication. A combination with immunosuppressive agents is currently utilized to reduce ADA development but is accompanied by an increased risk of side effects (i.e. malignancy and infections). The investigators have recently found an epidemiologic link between prior antibiotic use and the development of ADA, and shown an antibiotic-specific effect on ADA development in a mouse model. Macrolide antibiotics were specifically associated with ADA prevention and led to increased durability of the treatment. Since the microbiome has been associated with the response to anti-TNF therapy, the investigators hypothesize that microbial manipulation with azithromycin prior to the initiation of anti-TNF therapy will lower ADA development. the investigators propose a randomized controlled study to test our hypothesis and compare it to matched historical cohorts with available clinical and serological data. The primary outcome will be ADA development at 1 year of therapy.
1,992 studies on the registry are indexed under Crohn Disease; 478 are open to participants now.
This study's planned enrollment of 180 is above the median of 67 across 1,260 interventional studies indexed under Crohn Disease.
Browse Crohn Disease studies →Rambam Health Care Campus is the lead sponsor of 466 studies on the registry; 34 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
5-day consecutive treatment with oral azithromycin 500 mg once daily
Drug: Azithromycin Pill
5-day consecutive oral placebo once daily
Other: Placebo
Tablet - 500 mg azithromycin (as dihydrate)
Placebo tablet identical in shape and appearance to the azithromycin tablet used in the treatment arm
Anti-drug antibody development
Percent of patients developing anti-drug antibodies defined as measurable antibodies using an anti-lambda ELISA assay
Time frame: 1 year after the initiation of therapy
Sustained corticosteroid-free clinical remission
Crohn's Disease Activity Index (CDAI) ≤150 without systemic corticosteroid therapy
Time frame: At both 3 months and a 1 year after the initiation of therapy
Clinical response
A reduction in CDAI of at least 100 points from baseline.
Time frame: 1 year after the initiation of therapy
Sustained corticosteroid-free biochemical remission
C-reactive protein (CRP) ≤1.5 upper limit of normal, or fecal calprotectin ≤ 250 mg/kg
Time frame: at both 6 months and a 1 year after the initiation of therapy
Treatment durability
Persistent administration of infliximab or adalimumab for 1 year. A 16-week or more interval between infliximab injections, or an 8-week or more interval between adalimumab injections will be considered as treatment cessation. Change in anti-TNF regimen at 26 and 52 weeks defined as increased dosing or decreased dosing interval
Time frame: at both 6 months and a 1 year after the initiation of therapy
Anti-TNF drug levels
Levels at various timepoints
Time frame: At 6 weeks, 26 weeks and a 1 year after the initiation of therapy
Early anti-drug antibody development
Percent of patients developing anti-drug antibodies defined as measurable antibodies using an anti-lambda ELISA assay
Time frame: At 6 weeks, 26 weeks and a 1 year after the initiation of therapy
PRO-2 remission at Week 52
\- Patient reported outcome (PRO-2) remission at Week 52 (defined as an abdominal pain \[AP\] mean daily score at or below 1 \[AP≤1\] AND a stool frequency \[SF\] mean daily score at or below 3 \[SF≤3\], and no worsening of AP or SF from baseline).
Time frame: 1 year after the initiation of therapy
Sustained corticosteroid-free PRO-2 clinical remission
The rate of sustained corticosteroid-free PRO-2 clinical remission at both 14 and 52 weeks, defined as AP≤1 and SF≤3. The rate of clinical response at 14 weeks, defined as a reduction in CDAI of at least 100 points from baseline
Time frame: At both 14 and a 1 year after the initiation of therapy
Addition of immunomodulator treatment
The rate of addition of immunomodulator treatment defined as at least one dose of thiopurines or methotrexate
Time frame: At any time during the study
Immunomodulator treatment termination
The rate of immunomodulator treatment termination. Termination will be defined in patient treated with azathioprine or 6MP at randomization, as being stopped after at least 14 weeks and not restarting by 52 weeks
Time frame: At 14 weeks and not restarting by 1 year after the initiation of therapy
Endoscopic improvement
Endoscopic improvement defined as a reduction of ≥50% decrement from baseline in SES-CD score
Time frame: At 26 weeks
Endoscopic remission
Endoscopic remission defined as SES-CD ≤4
Time frame: At 26 and 52 weeks
Started Apr 2023 (actual). Primary completion is estimated for Sep 2026, 40 months after the start.
Of 82 phase 2 interventional studies under Crohn Disease, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 51. This study's planned 40 months is above that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Azithromycin