Slow and Low Start of a Tacrolimus Once Daily Immunosuppressive Regimen

NCT03672110 | Unknown Phase 3

• 1 other identifier: TUD-SplusL-061
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate non-inferiority of an advagraf based immunosuppressive regimen with slower dose tapering and lower starting dose of Advagraf compared with a standard Advagraf-based immunosuppressive regimen in de novo renal transplantation. Non inferiority will be assessed by a combined study endpoint consisting of the development of biopsy-proven rejection of BANFF class Ia or higher and/or graft loss and/or patient death within the first six months after renal transplantation.

Conditions

Renal Failure; Renal Insufficiency; Renal Disease; Renal Insufficiency, Chronic

Outcome Measures

Primary Outcomes (1)

• Combined endpoint: defined as biopsy-proven acute rejection, graft loss or death between the groups at month 6 post-transplantation in renal transplantation)

  combined endpoint: defined as biopsy-proven acute rejection, graft loss or death between the groups at month 6 post-transplantation in renal transplantation

  6 months after transplantation

Secondary Outcomes (25)

• Rate of necessary dose modifications to achieve Advagraf target levels in early post-op period

  6 months after transplantation

• Improved renal transplant function in the early postoperative period and 6 months post-op

  6 months after transplantation

• Lower incidence of delayed graft function (DGF)

  6 months after transplantation

• Reduced incidence of new onset diabetes after renal Transplantation (NODAT)

  6 months after transplantation

• Reduced rates of infection

  6 months after transplantation

Study Arms (2)

Standard tacrolimus group

ACTIVE COMPARATOR

Control group: Advagraf will be administered as usual (0.2mg/kg bodyweight), trough levels will be measured every day in the first week after kidney transplantation (TX) and Advagraf dose will be adjusted accordingly.

Drug: Advagraf

Fixed dose tacrolimus group

EXPERIMENTAL

Study group: Advagraf will be administered per fix dose 5mg/day, trough levels will be blinded during the first week, there will be no adjustments in the first week after TX.

Drug: Advagraf

Interventions

Advagraf DRUG

intervention: different advagraf dosing in the study compared to the control arm, see above

Also known as: no other intervention name

Fixed dose tacrolimus group; Standard tacrolimus group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male or female allograft recipients at least 18 years old
• primary or secondary kidney transplantation
• deceased or living donor
• normal immunological risk profile (PRA level \> 20%, AB0-compatible donation, negative crossmatch)
• informed consent of the patient

You may not qualify if:

• graft loss due to severe rejection within the first year after transplantation (in case of secondary transplantation)
• multi-organ recipient
• patients receiving a kidney from a non-beating donor
• complete human leukocyte antigen (HLA)-identical living donor (twins)
• patients with a history of malignancy during the last five years (except squamous or basal cell carcinoma of the skin after successful treatment)
• patients with uncontrolled infectious disease, particularly patients who are HIV-positive or suffer from chronic hepatitis B or C or tuberculosis
• patients with severe gastroenteric disorder, particularly severe diarrhea and symptoms of enteric malabsorption
• patients suffering from liver cirrhosis CHILD B or C or other severe liver disease (aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), GammaGT ≥ 3-fold increased)
• thrombopenia \< 70,000/mm3
• leukopenia \< 2,500/mm3
• estimated addiction or other disorders that do not allow the person concerned, the nature and scope and possible consequences of the clinical trial
• pregnant or breast-feeding women
• women of childbearing age, except women who meet any of the following criteria: post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum \> 40 U/ml, postoperatively (6 weeks after bilateral oophorectomy with or without hysterectomy), regular and correct use of a contraceptive method with error rate \< 1 % per year (e. g. implants, depot injections, oral contraceptives, intrauterine device IUD), sexual abstinence, vasectomy of the partner
• evidence that the patient is likely to fail to comply with the protocol (e. g. lack of cooperation)
• hypersensitivity to Advagraf or a product listed in the prescribing information other component as well as to other macrolides

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (1)

Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christian Hugo, MD, PhD

  TU Dresden

  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

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: September 14, 2018
• Study Start: September 1, 2014
• Primary Completion: February 1, 2020
• Study Completion: December 1, 2025
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

DE (1)