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. 2020 Aug 3;2020(8):CD012328. doi: 10.1002/14651858.CD012328.pub2

Ferrante 2015.

Study characteristics
Methods Multicentre randomised‐controlled trial conducted in Belgium, Czech Republic and Greece (4 centres) between 2005 and 2012.
Trial duration: 102 weeks
Participants Adults (16 to 75 years) undergoing bowel resection due to Crohn disease (resection of all macroscopic disease) with an endoscopically accessible anastomosis.
Participants with high risk of postoperative recurrence were included. High risk was defined as having one of the following risk factors:

  • Active inflammatory disease with C‐reactive protein elevation above 10 mg/L or the use of antibiotics, steroids or biologic therapy including anti‐TNF therapy for active ileal disease within 2 months before surgery

  • Perforating disease, defined as the presence of entero‐enteric or enterocutaneous fistulas or a perivisceral abscess formation within 2 months before surgery

  • Previous ileocolonic resection

  • Active smoking

  • Age <30 years


Control group
32 participants
Intervention group
31 participants
Interventions Control group
Initiation of prophylactic‐therapy within 14 days from surgery: Azathioprine (2.0 to 2.5 mg/kg per day).
Intervention group
No prophylactic‐therapy immediately after surgery
Colonoscopy at 26 and 102 weeks after surgery.
In case of endoscopic recurrence (Rutgeerts’ score ≥ i2), Azathioprine was introduced (2.0 to 2.5 mg/kg per day)
Outcomes Primary outcome
Endoscopic recurrence (Rutgeerts score ≥ i2)
Secondary outcomes
Clinical recurrence (CDAI > 150 points)
Surgical recurrence
Notes

  • This study was unblinded, however, endoscopists were blinded to treatment allocation and time interval from surgery.

  • The study was prematurely stopped due to slow recruitment.

  • The study was partially sponsored by the International Organization for the study of Inflammatory Bowel Disease (IOIBD).

  • The following authors declared these potential conflict of interest.

    • MF: financial support for research: Janssen Biologics; Lecture fees: Merck, Tillotts, Ferring, Abbvie, Boehringer Ingelheim; Consultancy: Abbvie, Merck, Janssen Biologics.

    • KP: Consultancy: MSD, Abbvie.

    • DD: Consultancy: MSD.

    • GDH: Financial support for research: Falk Pharma, MSD; Lecture fees: MSD, Takeda, Abbvie, Ferring; Consultancy: Janssen Biologics, MSD, Abbie, Shire Pharmaceuticals, Takeda, TEVA, Glaxo Smith Kline, Nova Nordisk, Pfizer, AM Pharma, Boehringer Ingelheim, Galapagos, Tillotts, Receptos, Salix, Setpoint, Versant.

    • SV: Financial support for research: UCB Pharma, Merck, Abbvie; Lecture fees: Abbvie, Merck, Ferring, UCB Pharma, Centocor; Consultancy: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, MSD.

    • PR: Financial support for research: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Bristol‐Myers Squibb; Lecture fees: Abbvie, Merck; Consultancy: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus, Pfizer, Falk Pharma, Tillotts.

    • GM: Financial support for research: Menarini, AstraZeneca; Lecture fees: MSD, AstraZeneca Pharmaceuticals, Falk Foundation, Abbvie, Angelini; Consultancy: Abbvie, MSD, Ferring Pharmaceuticals, Danon.

    • GVA: Financial support for research: Abbvie, Ferring; Lecture fees: Janssen‐Cilag, Merck, Abbvie; Consultancy: PDL BioPharma, UCB Pharma, Sanofi‐Aventis, Abbvie, Ferring; Novartis, Biogen Idec, Janssen Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis, BMS.

  • The following authors declared no conflicts of interest: EA and MB.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Computer‐generated randomisation in a 1:1 ratio.
Allocation concealment (selection bias) Low risk Participants were randomised 1:1 and balanced for age using a central computer‐based randomisation system.
Blinding of participants and personnel (performance bias)
All outcomes High risk Open‐label study.Participants and personnel were unblinded.
Blinding of outcome assessment (detection bias)
Clinical recurrence High risk Open‐label study. CDAI score has subjective items that are assessed by participants.
Blinding of outcome assessment (detection bias)
Endoscopic recurrence Low risk Endoscopists were blinded to treatment allocation and time interval from surgery.
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Withdrawals were balanced across the groups, the reasons were detailed, were not related to the outcomes and the analysis was according to the intention to treat principle. Despite this, the proportion of participants that dropped out was high (33.3%) and the effect estimate could be inaccurate.
Selective reporting (reporting bias) Unclear risk Primary and secondary outcomes were the same as in protocol published in ClinicalTrials.gov, number NCT02247258. Despite this, the protocol was submitted in Sep 2014, but the recruitment started in 2005 and was prematurely stopped due to slow recruitment.
Other bias Low risk Comment: No other major risk of bias was noticed