Condition category
Surgery
Date applied
16/07/2007
Date assigned
16/07/2007
Last edited
17/09/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ajda T Rowshani

ORCID ID

Contact details

Academic Medical Centre
Department of Internal Medicine
F4-215
P.O. Box 22700
Amsterdam
100 DE
Netherlands
+31 (0)20 566 3365 page 58816
T.Rowshani@amc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR1000

Study information

Scientific title

Acronym

AMC-DRIP

Study hypothesis

Donor-specific antibodies form a significant barrier in transplantation of highly pre-sensitised dialysis patients. Increased waiting time is associated with increased morbidity and mortality among these patients. Thus, there is a need to further develop desensitising therapies not only to make transplantation for this group of patients feasible, but also to reduce the occurrence of acute and chronic antibody-mediated graft damage caused by human leukocyte antigen (HLA) or non-HLA specific antibodies. Acute and chronic antibody-mediated graft damage is increasingly associated with decreased graft function and survival.

Ethics approval

Approval received from the Medical Ethics Committee of the Academic Medical Centre on the 15th February 2007 (ref: MEC 07/017# 07.17.0262).

Study design

A prospective, open, observational multi-centre clinical trial

Primary study design

Observational

Secondary study design

Multi-centre

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Highly sensitised renal transplant recipients

Intervention

In vivo administration of Rituximab (two doses):
The first dose of Rituximab (MabThera®, Roche) 375 mg/m^2 will be administered intravenously five months prior to the transplantation. The second and last dose will be administered before transplantation and after the completion of a successful treatment course with four doses of monthly IVIG administrations. The changes in the acceptable mismatch antigens will be analysed after each IVIG treatment course and the then extended profile of acceptable mismatches will be adjusted in the AM program. We expect that the patient can then be transplanted immediately or maximally up to six weeks thereafter.

Initial infusion: Start rate of 50 mg/hour; if there are no adverse side effects; increase the rate 50 mg/hour every 30 minutes, to a maximum of 400 mg/hour.

Subsequent infusions: Start at 100 mg/hour; if it is safe; increase the rate 100 mg/hour every 30 minutes, to a maximum of 400 mg/hour. All recipients will be given acetaminophen (1000 mg) and Di-adresoneF (25 mg), tavegil (2 mg), 30 minutes before the infusion.

In vivo administration of IVIG:
Intravenous administration of IVIG (IVIG-L, Nanogam, Sanquin) in a dose of 2 g/kg with a maximum of 140 gram, in a dilute, low-osmolaric solution. IVIG-L administration will be started at a speed of 30 ml/hr during the first 15 minutes. IVIG-L can be infused with infusion rates up to 8 ml/min (7 ml/kg/hr) without occurrence of severe side effects (Sanquin Clinical Study Report KB 97003B). In case of minor side effects, infusion will be withheld and after full clinical recovery of symptoms restarted at 50% of the original speed. To avoid the risk of over-hydration in dialysis patients, IVIG-L has to be given during dialysis in a 4-hour period and if necessary continued thereafter (dependent on the total dose which has to be infused), or otherwise IVIG-L infusion can be started on a not-dialysis day (dependent on the cardiovascular status of the patient and under clinical surveillance) followed by dialysis thereafter. No High Flux kidneys will be used in order to preserve and not to filter the administered IVIG.

Briefly, IVIG-L (2 g/kg; maximum dose: 140 g) will be administered, on dialysis or the day after, monthly maximally for 4 months with the last course one month before transplantation. If the patient who has completed the full desensitising treatment course has to wait longer than 4 weeks on the AM list in order to find a cross match negative organ, then another IVIG-L dose should be administered. The number of IVIG-L infusions depends on the results of the in vitro tests (PRA and CMX against unacceptable antigens) after each dose.

Plasmapheresis (PP):
If treatment consisting of the first dose of Rituximab and the full IVIG-L course of four monthly doses fail to achieve an acceptable low PRA and a negative cross-match (CMX) against the primarily unacceptable antigens, transplantation cannot take place. In this case we will institute a rescue plasmapheresis protocol encompassing maximal seven courses of daily large volume pheresis (40 ml/kg body weight) substituting plasma with saline/albumin solution in order to remove the antibodies, as it is known that a part of these patients can still respond to PP. If this occurs and the patient is eligible for transplantation, the second dose of Rituximab will be administered according to the protocol. After each third pheresis, plasma will be substituted with fresh frozen plasma (FFPs) in order to prevent and minimise the risk of bleeding.

Intervention type

Drug

Phase

Not Specified

Drug names

Rituximab, intravenous immunoglobulin-L

Primary outcome measures

Primary end-point is achievement of a negative cross-match test with the donor kidney and transplantability.

Secondary outcome measures

1. Patient and graft survival
2. Graft function as assessed by:
2.1. Calculated creatinine clearance
2.2. Proteinuria
2.3. The number and severity of acute (antibody mediated) rejections
2.4. Blood pressure (antihypertensive treatment)
2.5. Monitoring of infections
2.6. Occurrence of malignancies

Outcomes measured at six months after staring therapy and one year after transplantation.

Overall trial start date

15/07/2007

Overall trial end date

15/01/2010

Reason abandoned

Eligibility

Participant inclusion criteria

Patients older than 18 years with end stage renal failure and a current plasma renin activity (PRA) higher than 80% who are for more than two years on the waiting list for a cadaveric donor kidney, and included in the AM program. Only heart beating donors will be accepted.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

17

Participant exclusion criteria

1. Complete Immunoglobulin-A (IgA) deficiency
2. Over-hydration
3. History of anaphylaxis against blood/plasma products
4. Significant cardiac or pulmonary disease, hepatitis C or human immunodeficiency virus (HIV) infection, or malignancy within the last five years

Recruitment start date

15/07/2007

Recruitment end date

15/01/2010

Locations

Countries of recruitment

Netherlands

Trial participating centre

Academic Medical Centre
Amsterdam
100 DE
Netherlands

Sponsor information

Organisation

Academic Medical Centre (AMC) (The Netherlands)

Sponsor details

Department of Internal Medicine
P.O. Box 22660
Amsterdam
1100 DD
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.amc.uva.nl#http://www.amc.uva.nl/

Funders

Funder type

Hospital/treatment centre

Funder name

Academic Medical Centre (AMC) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes