NCT00316810

Brief Summary

The purpose of this study is to determine and compare the efficacy of Campath-1H/Tacrolimus versus ATG/Tacrolimus/MMF therapy in conjunction with initial short-term steroids in Type 1-diabetic patients undergoing simultaneous pancreas-kidney allograft transplantation as well as to evaluate the safety of Campath-1H/Tacrolimus versus ATG/Tacrolimus/MMF in terms of drug-related complications and immunosuppression-associated complications.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Apr 2006

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2006

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

April 19, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 21, 2006

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2011

Completed
Last Updated

June 19, 2012

Status Verified

June 1, 2012

Enrollment Period

4.8 years

First QC Date

April 19, 2006

Last Update Submit

June 18, 2012

Conditions

Pancreas-Kidney Transplantation

Keywords

Campath 1HAlemtuzumabTacrolimusPancreas-kidney transplantationimmunosuppressionprevention of acute rejection

Outcome Measures

Primary Outcomes (1)

  • Biopsy-proven (Kidney) rejection episodes

    Year 1

Secondary Outcomes (8)

  • Kidney/Pancreas function

    Month 6 and Year 1

  • Patient and graft survival

    Month 6 and Year 1

  • Lipid profile ( Total Cholesterol, HDL, LDL, Triglycerides, Treatment with statins)

    Month 6 and Year 1

  • Infections

    Month 6 and Year 1

  • Side effects

    Month 6 and Year 1

  • +3 more secondary outcomes

Study Arms (2)

Campath

EXPERIMENTAL

Day 0: Before revascularisation patients are given 500 mg of Methylprednisolone i.v. followed by Campath 30 mg i.v. infusion over 3-6 hours. Day 1: No treatment Day 2: Initial dose of Tacrolimus 0.05 - 0.1 mg/kg/d orally. till Month 6: Aim at blood level of 12-15 ng/ml (try to prevent the Tacrolimus trough level falling below 12 ng/ml in the first 6 months). Month 7-12: Maintain the Tacrolimus blood level at 6-12 ng/ml after 6 months.

Drug: Alemtuzumab

ATG

ACTIVE COMPARATOR

Day 0: Prior to revascularisation patients are given 500 mg of Methylprednisolone i.v. followed by a single shot of a polyclonal antilymphocyte preparation. Tacrolimus will be given immediately after transplantation(0.05-0.1 mg/kg/d) orally. Preoperative loading dose MMF: 2 g orally. From Day 1: Total initial daily dose of 0.05-0.1 mg/kg administered orally in 2 doses. Blood trough levels 12-15 ng/ml during the first 6 months and maintain blood levels 6-12 ng/ml after 6 months. Total daily dose of MMF is 2 g administered orally in 2 doses. Patients will receive Methylprednisolone 250 mg IV 12h post surgery and 125 mg of Methylprednisolone 24 h post transplantation. Steroid taper (orally): Day 2: 100 mg of Prednisolon Day 3: 80 mg of Prednisolon Day 4: 60 mg of Prednisolon Day 5: 40 mg of Prednisolon Day 6: 25 mg of Prednisolon Day 21: 20 mg of Prednisolon Reduction by 5 mg in two week intervals/complete withdrawal by 3 months post-tx.

Drug: Rabbit Anti-Human Thymocyte Globulin

Interventions

AlemtuzumabDRUG

Day 0: Campath 30 mg i.v. infusion over 3-6 hours

Also known as: MABCAMPATH
Campath
Rabbit Anti-Human Thymocyte GlobulinDRUG

Day O: Single shot of a polyclonal antilymphocyte preparation (ATG-Fresenius - 8 mg/kg, or IMTIX-Sangstat ATG 4 mg/kg/day).

Also known as: ATG-S FRESENIUS
ATG

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Male or female patients of 18 to 55 years of age with end-stage, C-peptide-negative, Type 1-diabetic nephropathy.
  • Female patients of childbearing age must have a negative pregnancy test and must agree to maintain effective birth control practice throughout the study period (3 years).
  • Patient must have signed the Patient Informed Consent Form.
  • Patient must receive a primary simultaneous pancreas-kidney (SPK) cadaveric transplant, with either intestinal or bladder and either portal or systemic venous drainages.

You may not qualify if:

  • Patient is pregnant or breastfeeding.
  • Patient is allergic or intolerant to Mycophenolate Mofetil, Tacrolimus or other macrolides, or any compounds structurally related to these compounds.
  • Past history of anaphylaxis following exposure to humanized monoclonal antibodies.
  • Patient has a positive T-cell crossmatch on the most recent serum specimen.
  • CMV-match: D+ / R-.
  • Patient is known for active liver disease or has significant liver disease; defined by ASAT and ALAT serum levels greater than 3 times the upper limit of normal.
  • Patient has malignancy or history of malignancy, with the exception of adequately treated localised squamous cell or basal cell carcinoma, without recurrence.
  • Patient has been included in another clinical trial protocol for any investigational drug within 4 weeks prior to randomisation.
  • Patient has any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may invalidate communication.
  • Patient receives a SPK transplant from a living donor, or receives segmental pancreatic transplant, or a previous kidney transplant alone.
  • Pancreatic duct occlusion technique.
  • Donor is older than 55 years of age.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Related Publications (8)

  • Robertson P, Davis C, Larsen J, Stratta R, Sutherland DE; American Diabetes Association. Pancreas transplantation in type 1 diabetes. Diabetes Care. 2004 Jan;27 Suppl 1:S105. doi: 10.2337/diacare.27.2007.s105. No abstract available.

    PMID: 14693941BACKGROUND

  • Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, Kandaswamy R, Mauer SM, Kennedy WR, Goetz FC, Robertson RP, Gruessner AC, Najarian JS. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001 Apr;233(4):463-501. doi: 10.1097/00000658-200104000-00003.

    PMID: 11303130BACKGROUND

  • Bechstein WO, Malaise J, Saudek F, Land W, Fernandez-Cruz L, Margreiter R, Nakache R, Secchi A, Vanrenterghem Y, Tyden G, Van Ophem D, Berney T, Boucek P, Landgraf R, Kahl A, Squifflet JP; EuroSPK Study Group. Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial. Transplantation. 2004 Apr 27;77(8):1221-8. doi: 10.1097/01.tp.0000120865.96360.df.

    PMID: 15114089BACKGROUND

  • Burke GW 3rd, Kaufman DB, Millis JM, Gaber AO, Johnson CP, Sutherland DE, Punch JD, Kahan BD, Schweitzer E, Langnas A, Perkins J, Scandling J, Concepcion W, Stegall MD, Schulak JA, Gores PF, Benedetti E, Danovitch G, Henning AK, Bartucci MR, Smith S, Fitzsimmons WE. Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results. Transplantation. 2004 Apr 27;77(8):1269-75. doi: 10.1097/01.tp.0000123903.12311.36.

    PMID: 15114097BACKGROUND

  • Stratta RJ, Alloway RR, Lo A, Hodge E. Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: primary endpoint analysis of a multicenter, randomized study. Transplantation. 2003 Apr 27;75(8):1260-6. doi: 10.1097/01.TP.0000062838.38351.2A.

    PMID: 12717213BACKGROUND

  • Kaufman DB, Leventhal JR, Gallon G, Axelrod D, Parker MA. Experience with Campath-1H induction therapy in simultaneous pancreas-kidney transplantation. Pancreas and Islet Transplant Association 2005, Geneva, Switzerland, [060]

    BACKGROUND

  • Thai NL, Khan A, Basu A, Tom K, Marcos A, Starzl TE, Shapiro R, Starzl TE. Pancreas transplantation under Campath-1H induction and tacrolimus monotherapy: preliminary results. The Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation, 2005, Seattle, USA, [433]

    BACKGROUND

  • Gruessner RW, Kandaswamy R, Humar A, Gruessner AC, Sutherland DE. Calcineurin inhibitor- and steroid-free immunosuppression in pancreas-kidney and solitary pancreas transplantation. Transplantation. 2005 May 15;79(9):1184-9. doi: 10.1097/01.tp.0000161221.17627.8a.

    PMID: 15880067BACKGROUND

MeSH Terms

Interventions

Alemtuzumabthymoglobulin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Johann Pratschke, Prof. Dr.

    University Hospital Innsbruck, Dept. of General- and Transplant Surgery, Anichstrasse 35, A-6020 Innsbruck

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Dr. med.

Study Record Dates

First Submitted

April 19, 2006

First Posted

April 21, 2006

Study Start

April 1, 2006

Primary Completion

February 1, 2011

Study Completion

June 1, 2011

Last Updated

June 19, 2012

Record last verified: 2012-06

Locations

AU(1)