Trial Title:
Pre-treatment With Azithromycin to Reduce Immunogenicity to to Anti-TNF Agents in Patients With Crohn's Disease
NCT ID:
NCT05599347
Condition:
Crohn's Disease Relapse
Biological Substance; Adverse Effect
Conditions: Official terms:
Crohn Disease
Azithromycin
Conditions: Keywords:
Crohn's disease
infliximab
adalimumab
azithromycin
immunogenicity
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
All consenting adults that fulfil the inclusion criteria will be randomized in a 1:1
ratio and allocated to the azithromycin or placebo arms
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
Double-blind masking
Intervention:
Intervention type:
Drug
Intervention name:
Azithromycin Pill
Description:
Tablet - 500 mg azithromycin (as dihydrate)
Arm group label:
Azithromycin
Intervention type:
Other
Intervention name:
Placebo
Description:
Placebo tablet identical in shape and appearance to the azithromycin tablet used in the
treatment arm
Arm group label:
Control
Summary:
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
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Ability to provide written informed consent prior to any study procedures and
willing and able to attend all study visits, comply with the study procedures, read
and write in order to complete questionnaires, and be able to complete the study
period.
- Aged 18 to 80 years of age, inclusive, at the time of signing the informed consent.
- Diagnosis of CD with an onset of symptoms for a minimum of 3 months prior to
Screening as determined by the investigator based on clinical history, exclusion of
infectious causes, and characteristic endoscopic and histologic findings.
- Prior decision of starting infliximab or adalimumab therapy (including biosimilar
drugs).
- Thiopurine and corticosteroid co-therapy will be permitted.
Exclusion Criteria:
- Inclusion in another interventional study
- Patients who cannot provide informed consent and do not have a legal guardian
- Patients with perianal involvement who are expected to require antibiotic therapy
for their disease
- Patients on chronic antibiotic therapy due to any cause
- Patients with ongoing fluid collection/abscess either internal or perianal
- Known history of allergy to the study intervention formulation or any of its
excipients or components of the delivery device
- Prolonged QTc interval or conditions leading to additional risk for QT prolongation
- Chronic kidney disease stage 5 (GFR < 10)
- Crohn's Disease complication requiring surgical treatment
- Planned/ongoing methotrexate co-therapy
- Fecal microbiota transplantation within 8 weeks prior to randomization
- Participant has any disorder that, in the opinion of the investigator, may
compromise the ability to participate in the study
- Pregnancy
- Patients who received azithromycin therapy in the previous year (we will not exclude
prior use of other antibiotic therapy)
- Patients who received any antibiotic treatment within 4 weeks prior to randomization
- Re-induction of the same anti-TNF medication
- Patients who are on chronic therapy which cannot be withheld in one of these
medications: colchicine, phenytoin, and digoxin
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Soroka University Medical Center
Address:
City:
Be'er Sheva
Country:
Israel
Status:
Not yet recruiting
Contact:
Last name:
Doron Schwartz, MD
Facility:
Name:
Hillel Yaffe Medical Center
Address:
City:
Hadera
Country:
Israel
Status:
Not yet recruiting
Contact:
Last name:
Baruch Ovadya, MD
Facility:
Name:
Bnei Zion
Address:
City:
Haifa
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Tova Rainis, MD
Facility:
Name:
Carmel Medical Center
Address:
City:
Haifa
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Ori Segol, MD
Facility:
Name:
Rambam Health Care Campus
Address:
City:
Haifa
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Haggai Bar-Yoseph, MD
Facility:
Name:
Wolfson Medical Center
Address:
City:
H̱olon
Country:
Israel
Status:
Not yet recruiting
Contact:
Last name:
Eran Israeli, MD
Facility:
Name:
Hadassah Medical Center
Address:
City:
Jerusalem
Country:
Israel
Status:
Not yet recruiting
Contact:
Last name:
Lior Katz, MD
Facility:
Name:
Shaare Zedek
Address:
City:
Jerusalem
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Ariella Shitrit, MD
Facility:
Name:
Zvulun
Address:
City:
Kiryat Bialik
Country:
Israel
Status:
Not yet recruiting
Contact:
Last name:
Reut Lutski, MD
Facility:
Name:
Rabin Medical Center
Address:
City:
Petah Tikva
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Iris Dotan
Facility:
Name:
el Aviv Sourasky Medical Center - Ichilov
Address:
City:
Tel Aviv
Country:
Israel
Status:
Not yet recruiting
Contact:
Last name:
Haim Leibovitzh, MD
Start date:
April 24, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Rambam Health Care Campus
Agency class:
Other
Source:
Rambam Health Care Campus
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05599347
