Clinical trial NCT02936505: Clinical Study Evaluating Two Treatment Protocols for Immunosuppressive Drugs. Looking at 3-year Incidence of CLAD.
Official title: A Scandinavian Controlled, Randomized, Open-label, and Multi-centre Study Evaluating if Once-daily Tacrolimus or Twice-daily Cyclosporin, Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Lung Transplantation
Allografts
Keywords: chronic lung allograft dysfunction
cyclosporin
tacrolimus
Bronchiolitis Obliterans Syndrome
Restrictive Allograft Syndrome
CLAD
immunization
renal function
survival
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Oslo University Hospital
name: Helsinki University Central Hospital
name: Skane University Hospital
name: Copenhagen University Hospital, Denmark
First posted: 2016-10-18
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A controlled randomized, open-label, multi-centre study evaluating if an immunosuppressive protocol, based on ATG-induction, once daily tacrolimus-dose (Advagraf®), mycophenolate mofetil and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after lung transplantation, in comparison with a standard cyclosporin-based protocol.

Detailed description: Study purpose:

To evaluate whether the use of a once-daily tacrolimus-dose regimen (Advagraf®), based on anti-thymocyte globulin (Thymoglobulin®) induction, mycophenolate mofetil (MMF) and corticosteroids, reduces the cumulative incidence of CLAD after de novo lung transplantation at 36 months, in comparison with a twice-daily cyclosporin-based protocol, otherwise identical between groups.

Eligibility criteria: Inclusion Criteria

1. Male or female lung recipients 18-70 years of age undergoing primary double (including size reduction) lung transplantation.
2. Patient willing and capable of giving written informed consent for study participation and anticipated to be able to participate in the study for 36 months.

Exclusion Criteria

1. Recipients of multiorgan transplant, and or previously transplanted with any organ, including previous lung transplantation.
2. Patients with hypersensitivity to, or other reasons to not be able to take the immunosuppressive drugs used in the study.
3. Donor lung cold ischemic time \> 12 hours.
4. Patients who previously have been treated with anti-thymocyte globulin preparations (e.g. ATG-Fresenius®, Thymoglobulin®).
5. Patients who are recipients of ABO-incompatible transplants.
6. Patients with platelet count \< 50,000/mm3 at the evaluation before transplantation.
7. Patients who are unlikely to comply with the study requirements.
8. Patients, and/or those receiving organs from donors, who are positive for HIV, Hepatitis B surface antigen or Hepatitis C virus.
9. Patients with donor greater than 75 years.
10. Patient who have received an unlicensed drug or therapy within one month prior to study entry or if such therapy is to be instituted post-transplantation.
11. Patient unable to participate in the study for the full 36-month period
12. Patients with any past (within the past 3-5 years) or present malignancy (other than excised basal cell carcinoma).
13. Females capable of becoming pregnant must have a negative pregnancy test prior to randomization.

Females are recommended to practice a medically approved method of birth control for the duration of the study and a period of 8 weeks following discontinuation of study medication, even where there has been a history of infertility

Primary outcomes:
measure: Number of patients with incidence of CLAD
timeFrame: 36 months is primary outcome
measure: Number of patients with incidence of CLAD
timeFrame: 48 months is outcome for the continuation study
measure: Number of patients with incidence of CLAD
timeFrame: 60 months is outcome for continuation study
measure: Number of patients with incidence of CLAD
timeFrame: 72 months is outcome for continuation study
Secondary outcomes:
measure: Glomerular Filtration Rate
timeFrame: 3 months
measure: Primary graft dysfunction
timeFrame: 72 hours
measure: Composite measure of freedom from AR, CLAD, graft and patient survival
timeFrame: 12 months
measure: Composite measure of freedom from AR, CLAD, graft and patient survival
timeFrame: 24 months
measure: Composite measure of freedom from AR, CLAD, graft and patient survival
timeFrame: 36 months
measure: Incidence of primary graft dysfunction
timeFrame: 72 hours
measure: Patient survival
timeFrame: 1 year
measure: Patient survival
timeFrame: 3 year
measure: Cumulative incidence of acute allograft rejection and CLAD
timeFrame: 6 months
measure: Cumulative incidence of acute allograft rejection and CLAD
timeFrame: 1 year
measure: Cumulative incidence of acute allograft rejection and CLAD
timeFrame: 3 year
measure: Cumulative incidence of BOS and RAS
timeFrame: 6 months
measure: Cumulative incidence of BOS and RAS
timeFrame: 1 year
measure: Cumulative incidence of BOS and RAS
timeFrame: 3 year
measure: Development of donor specific antibodies
timeFrame: 12 months
measure: Development of donor specific antibodies
timeFrame: 24 months
measure: Development of donor specific antibodies
timeFrame: 36 months
measure: Renal function mGFR
timeFrame: 12 months
measure: Renal function mGFR
timeFrame: 24 months
measure: Renal function mGFR
timeFrame: 36 months
measure: Renal function cGFR
timeFrame: 3 months
measure: Renal function cGFR
timeFrame: 12 months
measure: Renal function cGFR
timeFrame: 24 months
measure: Renal function cGFR
timeFrame: 36 months
measure: Post Transplantation Diabetes Mellitus
timeFrame: 6 months
measure: Post Transplantation Diabetes Mellitus
timeFrame: 12 months
measure: Post Transplantation Diabetes Mellitus
timeFrame: 24 months
measure: Post Transplantation Diabetes Mellitus
timeFrame: 36 months
measure: Antidiabetic medication
timeFrame: 6 months
measure: Antidiabetic medication
timeFrame: 12 months
measure: Antidiabetic medication
timeFrame: 24 months
measure: Antidiabetic medication
timeFrame: 36 months
measure: Antihypertensive and lipid lowering drugs
timeFrame: 12 months
measure: Antihypertensive and lipid lowering drugs
timeFrame: 24 months
measure: Antihypertensive and lipid lowering drugs
timeFrame: 36 months
measure: Proteinuria
timeFrame: 12 months
measure: Proteinuria
timeFrame: 24 months
measure: Proteinuria
timeFrame: 36 months
measure: Lipid profile
timeFrame: 12 months
measure: Lipid profile
timeFrame: 24 months
measure: Lipid profile
timeFrame: 36 months
measure: Cytomegalovirus
timeFrame: 0-36 months
measure: Malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers.
timeFrame: 36 months
measure: Safety and tolerability
timeFrame: 0-36 months
measure: Quality of life assessed by EQ5D Questionnaire
timeFrame: 12 months
measure: Quality of life assessed by St Georges Respiratory Questionnaire (SGRQ)
timeFrame: 12 months
measure: Quality of life, assessed by EQ5D Questionnaire
timeFrame: 24 months
measure: Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ)
timeFrame: 24 months
measure: Quality of life, assessed by EQ5D Questionnaire (SGRQ)
timeFrame: 36 months
measure: Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ)
timeFrame: 36 months
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population
timeFrame: week 4
measure: Pharmacokinetics of the Tacrolimus drug in patients in the CF sub group
timeFrame: 6 months
measure: Immunological equipotency of tacrolimus and cyclosporine A
timeFrame: 0-36 months
measure: Occurrence of treatment failures
timeFrame: 0-36 months
measure: Recovery of right heart function
timeFrame: 0-36 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska Univ Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
Study officials:
affiliation: Sahlgrenska Univ Hospital
name: Göran Dellgren, MD, PhD
role: STUDY_CHAIR
References:
citation: Dellgren G, Lund TK, Raivio P, Leuckfeld I, Svahn J, Magnusson J, Riise GC. Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study). Adv Ther. 2020 Mar;37(3):1260-1275. doi: 10.1007/s12325-020-01224-1. Epub 2020 Jan 28.