Evaluate the efficacy of the combination therapie with azithromycin and metronidazole in a randomized trial
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Response rate at 8 weeks defined as a drop in PCDAI of at least 12.5 points (or
remission without steroids, intention to treat principle)
Secondary outcome
Clinical remission defined in PCDAI less then 10
Background summary
Recent reviews and guidelines no longer recommend antibiotic therapy for
induction of remission in Crohn's disease (CD) due to studies showing lack of
efficacy. Genetic and microbiological findings have demonstrated that CD is
characterized by a defective innate immune response to bacteria and defective
apoptosis of T cells. Bacteria have been shown to reside on, and invade
epithelial cells, are present in granulomas and to replicate inside macrophage
phagolysosomes in susceptible individuals. A defect in bacterial triggering
from the luminal epithelial and intracellular compartments, while
simultaneously trying to induce apoptosis, has never been explored.
Azithromycin is an antibiotic with excellent intracellular penetration, high
luminal concentrations, and is also effective against biofilms which have been
described in CD. It is a potent activator of apoptosis of T cells. Preliminary
data in pediatric patients with short duration of disease have shown a
remission rate of 60% and normalization of CRP in about 50% of patients treated
with azithromycin and metronidazole in combination. We hypothesize that a
2-month antibiotic course of azithromycin combined with metronidazole is
effective for inducing remission in active pediatric Crohns disease (CD). We
also hypothesize that remission will be accompanied by normalization of CRP in
a high proportion of patients with active CD. The goal of the present study is
to evaluate the efficacy of this combination in a randomized controlled trial
(RCT).
Study objective
Evaluate the efficacy of the combination therapie with azithromycin and
metronidazole in a randomized trial
Study design
After inclusion and signed informed consent will be randomized eithe in group 1
(azithromycin and metronidazole) or group 2 (only metronidazole).
Intervention
Group 1: Oral Azithromycin 7.5 mg/kg once daily (maximum 500mg) 5 consecutive
days a week for the first 4 weeks and 3 consecutive days a week for the last 4
weeks
+ metronidazole 10mg/kg X2/day (maximum 1000mg) for 8 weeks
Group 2: Oral metronidazole 10mg/kg X2/day (maximum 1000mg) for 8 weeks
Study burden and risks
Risks associated with participation are minimal. We hypothesize that a 2-month
antibiotic course of azithromycin combined with metronidazole is effective for
inducing remission in active pediatric Crohns disease (CD). We also hypothesize
that remission will be accompanied by normalization of CRP in a high proportion
of patients with active CD.
HaLohamim Street 62
Holon 58100
IL
HaLohamim Street 62
Holon 58100
IL
Listed location countries
Age
Inclusion criteria
1. Children 5-17 years of age;2. Diagnosis of active Crohn's disease;3. Patients with a PCDAI equal of more then 10 and equal or less then 40 (mild to moderate disease);4. Have involvement of the colon and/or terminal ileum;5. Disease defined as L1, L2, L3 or any of the above and may have gastric, duodenal or esophageal disease (L4a) according to the paris classification for site of disease;6. The CRP is equal or more then 0.6 mg/dL;7. Duration of disease since diagnosis equal or less then 3 years;8. Negative stool culture, Clostridium Difficile Toxin from current flare
Exclusion criteria
1. Duration of disease since diagnosis more then 3 years.
2. Positive stool culture or O&P last 30 days.
3. Presence of clostridium difficile toxin in stool.
4. Azithromycin or Metronidazole allergy or known intolerance.
5. Diagnosis of IBD-U
6. Presence of macroscopic disease involving the proximal ileum or jejunum (L4b)
7. Continuous macroscopic disease of the colon appearing as typical ulcerative colitis and Crohns diagnosed only by focality or granuloma on biopsies.
8. Presence of extraintestinal manifestations (such as arthritis, uveitis, or sclerosing cholangitis). Apthous lesions of mouth can be included.
9. Presence of fibrostenotic disease (strictures with prestenotic dilatation).
10. Presence of penetrating disease (fistulas or abscess).
11. Presence of current perianal disease defined as fistula or abscess.
12. Patients receiving concurrent corticosteroids or biologics.
13. Patients who have received steroids in the past 14 days.
14. Immune deficiency (CGD, GSD1, IL10R etc).
15. Known allergy or intolerance to any of the study medications.
16. Concurrent disease such as hepatitis, ALT more then 2 times, UNL, renal failure.
17. Pregnancy,
18. Patients with known heart disease.
19. Prolonged QTc by ECG at baseline.
20. Patients after surgical intestinal resection.
21. Present use of medications known to prolong QTc, such as cisapride, terfenadine, domperidone, erythromycin, and ergotamines.
22. Present use of acenocoumarol or digoxin.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-005226-29-NL |
| ClinicalTrials.gov | NCT01596894 |
| CCMO | NL42267.078.12 |