RITUX-ERAH: Impact of Treatment With Rituximab on the Progression of Humoral Acute Rejection After Renal Transplantation

Sponsor

University Hospital, Tours (Other)

Overall Status

Unknown status

CT.gov ID

NCT01066689

Collaborator

Roche Pharma AG (Industry)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Assessing the impact of J12 curative treatment with rituximab (375 mg / m² on J5) based on a composite "TREATMENT FAILURE"

Condition or Disease	Intervention/Treatment	Phase
Graft Rejection	Drug: MabThera Drug: Physiological serum (Sodium Chloride, sodium citrate)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase III Study of Impact of Treatment With Rituximab on the Progression of Humoral Acute Rejection After Renal Transplantation.

Study Start Date :

Oct 1, 2008

Anticipated Primary Completion Date :

Oct 1, 2011

Anticipated Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Patients randomized into the arm blind A. Rituximab is allowed as additional treatment from J12, within the limit of 2 infusions of rituximab. In case of insufficient efficacy of the treatment of acute humoral rejection, investigators may propose an additional infusion of rituximab from J12, without patient withdrawn. In this case (2nd infusion effective in group A and 1st infusion effective group B), a additional consultation (CS) will be provided as part of the study 7 days after infusion. In case of insufficient efficacy of the treatment,in fairness to care for patients between the 2 treatment groups, the investigators may propose to a 3rd infusion patients in group B (2nd infusion effective for this group). To prevent patients from group A will receive a 3rd infusion of rituximab, unblinding will be applied in this case by the investigator before the administration of additional treatment with rituximab.	Drug: MabThera MabThera 500mg/50ml I.V. infusion, single dose : 375 mg/m2 Other Names: rituximab
Placebo Comparator: B Patients randomized into the arm blind B. Rituximab is allowed as additional treatment from J12, within the limit of 2 infusions of rituximab. In case of insufficient efficacy of the treatment of acute humoral rejection, investigators may propose an additional infusion of rituximab from J12, without patient withdrawn. In this case (2nd infusion effective in group A and 1st infusion effective group B), a additional consultation (CS) will be provided as part of the study 7 days after infusion. In case of insufficient efficacy of the treatment,in fairness to care for patients between the 2 treatment groups, the investigators may propose to a 3rd infusion patients in group B (2nd infusion effective for this group). To prevent patients from group A will receive a 3rd infusion of rituximab, unblinding will be applied in this case by the investigator before the administration of additional treatment with rituximab.	Drug: Physiological serum (Sodium Chloride, sodium citrate) Solution for I.V. infusion Sodium Chloride (pH 6.5), polysorbate 80, sodium citrate (10.0mg/ml)

Arm

Intervention/Treatment

Experimental: A

Patients randomized into the arm blind A. Rituximab is allowed as additional treatment from J12, within the limit of 2 infusions of rituximab. In case of insufficient efficacy of the treatment of acute humoral rejection, investigators may propose an additional infusion of rituximab from J12, without patient withdrawn. In this case (2nd infusion effective in group A and 1st infusion effective group B), a additional consultation (CS) will be provided as part of the study 7 days after infusion. In case of insufficient efficacy of the treatment,in fairness to care for patients between the 2 treatment groups, the investigators may propose to a 3rd infusion patients in group B (2nd infusion effective for this group). To prevent patients from group A will receive a 3rd infusion of rituximab, unblinding will be applied in this case by the investigator before the administration of additional treatment with rituximab.

Drug: MabThera

MabThera 500mg/50ml I.V. infusion, single dose : 375 mg/m2

Other Names:

rituximab

Placebo Comparator: B

Patients randomized into the arm blind B. Rituximab is allowed as additional treatment from J12, within the limit of 2 infusions of rituximab. In case of insufficient efficacy of the treatment of acute humoral rejection, investigators may propose an additional infusion of rituximab from J12, without patient withdrawn. In this case (2nd infusion effective in group A and 1st infusion effective group B), a additional consultation (CS) will be provided as part of the study 7 days after infusion. In case of insufficient efficacy of the treatment,in fairness to care for patients between the 2 treatment groups, the investigators may propose to a 3rd infusion patients in group B (2nd infusion effective for this group). To prevent patients from group A will receive a 3rd infusion of rituximab, unblinding will be applied in this case by the investigator before the administration of additional treatment with rituximab.

Drug: Physiological serum (Sodium Chloride, sodium citrate)

Solution for I.V. infusion Sodium Chloride (pH 6.5), polysorbate 80, sodium citrate (10.0mg/ml)

Outcome Measures

Primary Outcome Measures

"Treatment failure" grouping at J12: - Loss of graft - Whether improving renal function (defined by the absence of a decrease in creatinine of at least 30% compared to the maximum serum creatinine reached at the RAH) [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient adult male or female (age 18 years), kidney transplantation for less than one year (transplant from a living donor or deceased), with acute humoral rejection defined by :
The deterioration of renal function assessed by serum creatinine increase of more than 20% compared to the best value, OR
In the first 28 days after transplantation, no significant creatinine decrease, AND
At least 2 of the 3 following criteria:
tissue damage such as (a) acute tubular necrosis, (b) presence of monocytes or granulocytes in the CPT and / or glomeruli and / or capillary thrombosis, (c) intimal arteritis / fibrinoid necrosis
C4d level of CPT and / or presence of Ig or complement in lesions of fibrinoid necrosis
Presence of HLA antibodies directed against the donor. Patient having given his written consent to participate in the clinical trial.

Exclusion Criteria:

Pregnant or lactating
Women during their reproductive years without effective contraception,
A patient with multiple organ transplants,
Patients with clinically active infection by HCV uncontrolled
Patients with active infection, or suspected of infection by HIV or HBV, and tuberculosis,
Patients with heart failure class IV (NYHA) cardiac disease or uncontrolled
Patients for whom vaccination is scheduled,
Patient with disabilities did not allow an understanding of the requirements of the test
Patient in safeguarding justice, guardianship or trusteeship,
Patient with cons-indication to rituximab (known hypersensitivity to any component or murine protein)
Patient had previously received rituximab within 3 months before inclusion
Patient participation in another clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Henri Mondor	Paris	Créteil	France	94010
2	Hospital	Grenoble	La Tronche	France	38700
3	Hospital Bicêtre	Paris	Le Kremlin Bicêtre	France	94275
4	Hospital Lyon Sud	Lyon	Pierre-Benite	France	69495
5	Hospital Nord	Saint-Etienne	Saint Priez-en-Jarez	France	42227
6	Hospital Foch	Paris	Suresnes	France	92151
7	Hospital Nancy-Brabois	Nancy	Vandoeuvre-les-Nancy	France	54511
8	Hospital Sud	Amiens		France	80054
9	Hospital	Angers		France	49933
10	Hospital Saint-Jacques	Besancon		France	25030
11	Hospital Pellegrin	Bordeaux		France	33076
12	Hospital	Brest		France	29609
13	Hospital	Caen		France	14033
14	Hospital Gabriel Montpied	Clermont-ferrand		France	63003
15	Hospital Bocage	Dijon		France	21000
16	Hospital Calmette	Lille		France	59037
17	Hospital Dupuytren	Limoges		France	87042
18	Hospital Edouard Herriot	Lyon		France	69437
19	Hospital Conception	Marseille		France	13385
20	Hospital Lapeyronie	Montpellier		France	34295
21	Hospital Hôtel Dieu	Nantes		France	44093
22	Hospital Pasteur	Nice		France	06000
23	Hospital Saint Louis	Paris		France	75000
24	Hospital Tenon	Paris		France	75020
25	Hospital Pitié-Salpêtrière	Paris		France	75651
26	Hospital Necker	Paris		France	75743
27	Hospital Milétrie Jean Bernard	Poitiers		France	86021
28	Hospital Maison Blanche	Reims		France	51092
29	Hospital	Rennes		France	35033
30	Hospital Bois-Guillaume	Rouen		France	76231
31	Hospital Civil	Strasbourg		France	67091
32	Hospital Bretonneau	Tours		France	37044

Sponsors and Collaborators

University Hospital, Tours
Roche Pharma AG

Investigators

Principal Investigator: Yvon LEBRANCHU, University Hospital, Tours

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT01066689

Other Study ID Numbers:

PHRN07-YL RITUX-ERAH

First Posted:

Feb 10, 2010

Last Update Posted:

Feb 10, 2010

Last Verified:

Feb 1, 2010

Keywords provided by , ,

kidney transplantation, acute humoral rejection, rituximab

Additional relevant MeSH terms:

Rituximab

Citric Acid

Sodium Citrate

Study Results

No Results Posted as of Feb 10, 2010