Clinical trial NCT00528073: Placebo Controlled Study of 3 Doses of Rifaximin-EIR Tablet to Treat Moderate, Active Crohn's Disease
Official title: A Phase II, Multicentre, Double-blind, Randomised, Dose Range Finding Placebo Controlled Study of Rifaximin-EIR Tablet: Clinical Effectiveness and Tolerability in the Treatment of Moderate, Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Rifaximin-EIR
Crohn's disease
remission
Lead sponsor: Alfasigma S.p.A.
Sponsor class: INDUSTRY
First posted: 2007-09-11
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to determine which of 3 doses of a non-absorbable antibiotic Rifaximin is most effective in treating active moderate Crohn's disease. Rifaximin tablets are already marketed in some European countries and the USA to treat traveller's diarrhoea. A new gastro-resistant form of Rifaximin called Rifaximin-Extended Intestinal Release (EIR) will be used in this study. These tablets dissolve in the stomach,releasing gastro-resistant granules which pass into the intestines and deliver Rifaximin directly to the site of the disease. Rifaximin is not absorbed, making it more effective and greatly reducing the frequency of side effects.


Eligibility criteria: Inclusion Criteria:

* diagnosis of Crohn's disease localised in the ileum and/or colon, documented either radiologically or endoscopically at least 3 months previously;
* patients with a CDAI of ≥ 220 to ≤ 400;
* patients capable of and willing to conform to the study protocol;
* patients who have provided signed and dated written informed consent.

Exclusion Criteria:

* patients potentially needing immediate surgery for Crohn's disease, including patients with occlusive symptoms and/or stenotic tract with dilation above;
* patients with active perianal Crohn's disease;
* patients with other infectious, ischemic, or immunological diseases with gastrointestinal involvement;
* patients with symptoms attributed to Short Bowel Syndrome or previous surgery;
* patients with stoma;
* patients affected by upper gastro-intestinal disease (gastro-duodenum-jejunum Crohn's disease) alone or in combination with colitis or ileitis;
* patients treated with: oral steroids and budesonide less than 30 days prior to screening; i.v. steroids less than 30 days prior to screening; antibiotics (such as metronidazole, tinidazole, ciprofloxacin, clarithromycin) less than 15 days prior to screening;
* rectal steroids less than 30 days prior to the screening visit;
* anti-tumour necrosis factor (anti-TNF) and other biological therapies less than 6 months prior to the screening visit;
* pregnant women or nursing mothers;
* females of childbearing age (unless surgically sterile) without a negative urine pregnancy test at screening and at enrolment;
* patients with severe hepatic insufficiency (Child C);
* patients with severe cardiac insufficiency (NYHA - New York Heart Association classes 3 - 4);
* patients with known hypersensitivity to Rifaximin;
* any condition or circumstance that would prevent completion of the study or interfere with analysis of study results, including a history of drug or alcohol abuse, mental illness or non-compliance with treatments or visits, with immunological (including HIV infection), haematological or neoplastic disease;
* withdrawal of informed consent;
* patients who have used any investigational drug (except biological therapies) within 3 months prior to screening;
* patients who have donated 250 ml or more of blood in the last 3 months.

Primary outcomes:
measure: Clinical remission (Crohn's Disease Activity Index < 150 points)
timeFrame: After 12 weeks of treatment
Secondary outcomes:
measure: Clinical response (reduction of baseline CDAI score by 100 points or more)
timeFrame: Any time during the 12 weeks of treament
measure: Clinical response (reduction of baseline CDAI by 70 points or more)
timeFrame: At any time during the 12 weeks of treatment
measure: Time to obtain clinical response and remission
timeFrame: During the 12 weeks of treatment
measure: Maintenance of clinical remission
timeFrame: 2 weeks after the end of the 12 weeks of treatment
measure: Maintenance of clinical remission
timeFrame: 12 weeks after the end of the 12 weeks of treatment
measure: Number of treatment failures
timeFrame: During the 12 weeks of treatment
measure: Definition of therapeutic dose to be used in subsequent phase III trials.
timeFrame: After statistical analysis of the results
measure: Adverse events
timeFrame: Throughout the study
Other outcomes:
Locations:
city: Amiens Cedex
country: France
facility: CHU Amiens, Hôpital Nord
city: Bordeaux Cedex
country: France
facility: Hôpital Saint André
city: Grenoble Cedex 9
country: France
facility: CHU Grenoble, Hôpital Michallon
city: Nice Cedex 3
country: France
facility: CHU de Nice, Hôpital de l'Archet II
city: Rouen
country: France
facility: CHU de Rouen, Hôpital Charles Nicolle
city: Berlin
country: Germany
facility: Charité Campus Mitte
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Frankfurt/Main
country: Germany
facility: Interdisziplinäres Facharztzentrum, Zentrum für Viszerale- und Ernährungsmedizin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hindenburgdamm 30, Berlin
country: Germany
facility: Abteilung Gastroenterologie, Charité Campus Benjamin Franklin
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: Minden
country: Germany
facility: Gastroenterological Group Practice
city: Budapest
country: Hungary
facility: Allami Egeszsegugyi Kozpont, MAV-Rendeszeti Szervek-Honvedseg Egyesitett Korhaza
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos és Egészégtudományi Centrum II. Belgyógyászati Klinika
city: Gyula
country: Hungary
facility: Békés Megyei Kèpviselőtestület, Pándy Kálmán Kórház, III. Belgyógyászat
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem, Általános Orvostudományi Kar, I. sz. Belgyógyászati Klinika
city: Szekszárd
country: Hungary
facility: Tolna Megyei Önkormányzat Balassa János Kórhaz, II. Belgyógyászat
city: Vác
country: Hungary
facility: Jávorszky Ödön Kórház, Gasztroenterológiai Osztály
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Petah Tiqwa
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza IRCCS
state: Foggia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Bologna
country: Italy
facility: Azienda Ospedaliera-Universitaria di Bologna - Policlinico S. Orsola-Malpighi
city: Milan
country: Italy
facility: A.O. Luigio Sacco U.O gastraneterologia, via G.B. grassi 74
city: Padova
country: Italy
facility: Azienda Ospedaliera Padova
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico di Torvergata
city: Rome
country: Italy
facility: Azienda Ospedaliera "San Camillo-Forlanini"
city: Rome
country: Italy
facility: Policlinico "A,. Gemelli"
city: Turin
country: Italy
facility: Azienda Ospedaliera S. Giovanni Battista Molinette
city: Turin
country: Italy
facility: Ospedale Mauriziano "Umberto I"
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Polikliniką
city: Częstochowa
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. Najświętszej Maryi Panny
city: Gdańsk
country: Poland
facility: Szpital Specjalistyczny Św. Wojciecha- Adalberta
city: Katowice
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny Im Prof. Kornela Gibinskiego Ślaskiej Akademii Medycznej
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
city: Wroclaw
country: Poland
facility: Akademicki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego
city: Krasnodar
country: Russian Federation
facility: Russian Center of Functional Surgical Gastroenterology
city: Moscow
country: Russian Federation
facility: Sechenov Moscow Medical Academy
city: Moscow
country: Russian Federation
facility: State Scientific Centre of Coloproctology
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 24
city: Moscow
country: Russian Federation
facility: Moscow Regional Research Clinical Institute n.a. M.F. Vladimirsky
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Regional Clinical Hospital
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Medical University City Hospital #7
city: Rostov-na-Donu
country: Russian Federation
facility: Rostov State Medical University City Hospital # 20
city: St. Petersburg
country: Russian Federation
facility: City Polyclinic # 38
city: St. Petersburg
country: Russian Federation
facility: Military Medical Academy
city: St. Petersburg
country: Russian Federation
facility: Sokolov Clinical Hospital #122
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Mechnikov State Medical Academy
city: St. Petersburg
country: Russian Federation
facility: MAPO, City Hospital # 26
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg MAPO, City Hospital #31
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
Study officials:
affiliation: Alfa Wassermann
name: Pier Alessandro Monici Preti, MD
role: STUDY_CHAIR
affiliation: Alfa Wassermann
name: Maria Grimaldi, MD
role: STUDY_DIRECTOR
affiliation: S. Camillo - Forlanini Hospital
name: Cosimo Prantera, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prantera C, Lochs H, Campieri M, Scribano ML, Sturniolo GC, Castiglione F, Cottone M. Antibiotic treatment of Crohn's disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin. Aliment Pharmacol Ther. 2006 Apr 15;23(8):1117-25. doi: 10.1111/j.1365-2036.2006.02879.x.
citation: Prantera C, Lochs H, Grimaldi M, Danese S, Scribano ML, Gionchetti P; Retic Study Group (Rifaximin-Eir Treatment in Crohn's Disease). Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease. Gastroenterology. 2012 Mar;142(3):473-481.e4. doi: 10.1053/j.gastro.2011.11.032. Epub 2011 Dec 6.