The DRIP Study: desensitisation of highly pre-sensitised dialysis patients waiting for kidney transplantation by Rituximab, Intravenous Immunoglobulin-L (IVIG-L) and rescue Plasmapheresis (AMC-DRIP)
| ISRCTN | ISRCTN76326553 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76326553 |
| Secondary identifying numbers | NTR1000 |
- Submission date
- 16/07/2007
- Registration date
- 16/07/2007
- Last edited
- 17/09/2008
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Ajda T Rowshani
Scientific
Scientific
Academic Medical Centre
Department of Internal Medicine, F4-215
P.O. Box 22700
Amsterdam
100 DE
Netherlands
| Phone | +31 (0)20 566 3365 page 58816 |
|---|---|
| T.Rowshani@amc.nl |
Study information
| Study design | A prospective, open, observational multi-centre clinical trial |
|---|---|
| Primary study design | Observational |
| Secondary study design | Multi-centre |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study acronym | AMC-DRIP |
| Study objectives | 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(s) | Approval received from the Medical Ethics Committee of the Academic Medical Centre on the 15th February 2007 (ref: MEC 07/017# 07.17.0262). |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Rituximab, intravenous immunoglobulin-L |
| Primary outcome measure | 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 study start date | 15/07/2007 |
| Completion date | 15/01/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 17 |
| Key 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. |
| Key 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 |
| Date of first enrolment | 15/07/2007 |
| Date of final enrolment | 15/01/2010 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Academic Medical Centre
Amsterdam
100 DE
Netherlands
100 DE
Netherlands
Sponsor information
Academic Medical Centre (AMC) (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Department of Internal Medicine
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
| Website | http://www.amc.uva.nl#http://www.amc.uva.nl/ |
|---|---|
"ROR" |
https://ror.org/03t4gr691 |
Funders
Funder type
Hospital/treatment centre
Academic Medical Centre (AMC) (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
