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Active, Not Recruiting

NCT Number: NCT02936505

Clinical Study Evaluating Two Treatment Protocols for Immunosuppressive Drugs. Looking at 3-year Incidence of CLAD.

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Lung Transplantation Allografts Bronchial Diseases Bronchiolitis Bronchiolitis Obliterans Bronchiolitis Obliterans Syndrome Bronchitis Graft vs Host Disease Immune System Diseases Lung Diseases Lung Diseases, Obstructive Organizing Pneumonia Respiratory Tract Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Rigshospitalet, Copenhagen, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female lung recipients 18-70 years of age undergoing primary double (including size reduction) lung transplantation.
  • 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

  • Recipients of multiorgan transplant, and or previously transplanted with any organ, including previous lung transplantation.
  • Patients with hypersensitivity to, or other reasons to not be able to take the immunosuppressive drugs used in the study.
  • Donor lung cold ischemic time > 12 hours.
  • Patients who previously have been treated with anti-thymocyte globulin preparations (e.g. ATG-Fresenius®, Thymoglobulin®).
  • Patients who are recipients of ABO-incompatible transplants.
  • Patients with platelet count < 50,000/mm3 at the evaluation before transplantation.
  • Patients who are unlikely to comply with the study requirements.
  • Patients, and/or those receiving organs from donors, who are positive for HIV, Hepatitis B surface antigen or Hepatitis C virus.
  • Patients with donor greater than 75 years.
  • 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.
  • Patient unable to participate in the study for the full 36-month period
  • Patients with any past (within the past 3-5 years) or present malignancy (other than excised basal cell carcinoma).
  • 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

Treatment and study plan

cyclosporine

Drug

Cyclosporin A (Sandimmun Neoral® or similar):

  • Cyclosporin A given orally pretransplant in the dose of 2-3 mg/kg.
  • Continued postop day 1 in the dose of 3mg/kgx2, according to local practice and blood concentration: 0-3 months 250-300; 3-6 months 200-250; 6-12 months 150-200; >12 months 100-150 ng/ml. Cyclosporine A will be administered twice daily.

Other names: Sandimmun Neural

Mycophenolate Mofetil (MMF)

Drug

MMF target dose: 2000 mg/day (1gx2):

o Controlled by a single Area Under the Curve (AUC) measurement day 90 with a target AUC between 40 and 60 mg.h/L and corrected accordingly.

Other names: Cellcept

Rabbit Anti thymocyte globulin

Drug

Induction therapy: Thymoglobulin® (Rabbit Anti thymocyte globulin)(1.5 mg/kg given immediately postoperatively).

Other names: Thymoglobulin®

Corticosteroids

Drug

Corticosteroids:

  • Day 0 (day of lung transplantation); 500+500mg methylprednisolone iv. before reperfusion, i.e. restoration of blood flow into the transplanted allograft.
  • From day 1: Initiated at 0.2 mg/kg/day; tapered to 0.1 mg/kg 3-6 months; less than 0,1 mg/kg > 6 months.

Other names: Methylprednisolon

Tacrolimus

Drug
  • Tacrolimus should be given orally pretransplant in the dose of 0.1 mg/kg.
  • Continued postop day 1 according to local practice and blood concentration: 0-3 months 10-14, 3-6 months 8-12, 6-12 months 8-10, >12 months 6-8 ng/ml. Tacrolimus will be administered once daily.

Other names: Advagraf®

Primary outcomes

  1. Number of patients with incidence of CLAD

    Time frame: 36 months is primary outcome

    The cumulative incidence of CLAD (including both BOS and RAS, as defined in the Appendix II) after lung transplantation.

  2. Number of patients with incidence of CLAD

    Time frame: 48 months is outcome for the continuation study

    The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 48 months after lung transplantation.

  3. Number of patients with incidence of CLAD

    Time frame: 60 months is outcome for continuation study

    The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 60 months after lung transplantation.

  4. Number of patients with incidence of CLAD

    Time frame: 72 months is outcome for continuation study

    The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 72 months after lung transplantation.

Secondary outcomes

  1. Glomerular Filtration Rate

    Time frame: 3 months

    Renal function evaluated by measured glomerular filtration rate

  2. Primary graft dysfunction

    Time frame: 72 hours

    Cumulative incidence of primary graft dysfunction

  3. Composite measure of freedom from AR, CLAD, graft and patient survival

    Time frame: 12 months

    Composite measure of freedom from first event of AR, CLAD, graft survival, and patient survival

  4. Composite measure of freedom from AR, CLAD, graft and patient survival

    Time frame: 24 months

    Composite measure of freedom from first event of AR, CLAD, graft survival, and patient

  5. Composite measure of freedom from AR, CLAD, graft and patient survival

    Time frame: 36 months

    Composite measure of freedom from first event of AR, CLAD, graft survival, and patient

  6. Incidence of primary graft dysfunction

    Time frame: 72 hours

    cumulative incidence of primary graft dysfunction

  7. Patient survival

    Time frame: 1 year

    Patient survival

  8. Patient survival

    Time frame: 3 year

    Patient survival

  9. Cumulative incidence of acute allograft rejection and CLAD

    Time frame: 6 months

    The cumulative incidence of acute allograft rejection (AR) and CLAD. - Determined by clinical criteria, computed tomography (CT) and trans bronchial lung biopsy with broncho-alveolar lavage (BAL). - Number of rejections (cellular and antibody mediated), stratified by biopsy and non-biopsy verified rejections.

  10. Cumulative incidence of acute allograft rejection and CLAD

    Time frame: 1 year

    The cumulative incidence of acute allograft rejection (AR) and CLAD. - Determined by clinical criteria, computed tomography (CT) and trans bronchial lung biopsy with broncho-alveolar lavage (BAL). - Number of rejections (cellular and antibody mediated), stratified by biopsy and non-biopsy verified rejections.

  11. Cumulative incidence of acute allograft rejection and CLAD

    Time frame: 3 year

    The cumulative incidence of acute allograft rejection (AR) and CLAD. - Determined by clinical criteria, computed tomography (CT) and trans bronchial lung biopsy with broncho-alveolar lavage (BAL). - Number of rejections (cellular and antibody mediated), stratified by biopsy and non-biopsy verified rejections.

  12. Cumulative incidence of BOS and RAS

    Time frame: 6 months

    The cumulative incidence of BOS and RAS

  13. Cumulative incidence of BOS and RAS

    Time frame: 1 year

    The cumulative incidence of BOS and RAS

  14. Cumulative incidence of BOS and RAS

    Time frame: 3 year

    The cumulative incidence of BOS and RAS

  15. Development of donor specific antibodies

    Time frame: 12 months

    Development of donor specific antibodies (DSA) according to specific protocol.

  16. Development of donor specific antibodies

    Time frame: 24 months

    Development of donor specific antibodies (DSA) according to specific protocol.

  17. Development of donor specific antibodies

    Time frame: 36 months

    Development of donor specific antibodies (DSA) according to specific protocol.

  18. Renal function mGFR

    Time frame: 12 months

    Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance.

  19. Renal function mGFR

    Time frame: 24 months

    Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance.

  20. Renal function mGFR

    Time frame: 36 months

    Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance.

  21. Renal function cGFR

    Time frame: 3 months

    Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas.

  22. Renal function cGFR

    Time frame: 12 months

    Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas.

  23. Renal function cGFR

    Time frame: 24 months

    Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas.

  24. Renal function cGFR

    Time frame: 36 months

    Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas.

  25. Post Transplantation Diabetes Mellitus

    Time frame: 6 months

    The cumulative incidence of Post Transplantation Diabetes Mellitus (PTDM) after transplantation as defined below. Cumulative incidence of

    ≥2 Fasting Plasma Glucose (FPG) ≥7,0 mmol/L ≥ 30 consecutive days apart. Oral hypoglycaemic treatment ≥30 consecutive days. Insulin ≥30 consecutive days. HgbA1c ≥6.5% (according to American Diabetes Association - ADA)Symptoms of Diabetes and Random Plasma Glucose (RPG) ≥ 11.1 mmol/L.

    2-hour Plasma Glucose (2-hPG) ≥ 11.1 mmol/L during an oral glucose tolerance test (OGTT). Baseline OGTT will be performed pre-transplant.

  26. Post Transplantation Diabetes Mellitus

    Time frame: 12 months

    The cumulative incidence of Post Transplantation Diabetes Mellitus (PTDM) after transplantation as defined below. Cumulative incidence of

    ≥2 Fasting Plasma Glucose (FPG) ≥7,0 mmol/L ≥ 30 consecutive days apart. Oral hypoglycaemic treatment ≥30 consecutive days. Insulin ≥30 consecutive days. HgbA1c ≥6.5% (according to American Diabetes Association - ADA) Symptoms of Diabetes and Random Plasma Glucose (RPG) ≥ 11.1 mmol/L. 2-hour Plasma Glucose (2-hPG) ≥ 11.1 mmol/L during an oral glucose tolerance test (OGTT). Baseline OGTT will be performed pre-transplant.

  27. Post Transplantation Diabetes Mellitus

    Time frame: 24 months

    The cumulative incidence of Post Transplantation Diabetes Mellitus (PTDM) after transplantation as defined below. Cumulative incidence of

    ≥2 Fasting Plasma Glucose (FPG) ≥7,0 mmol/L ≥ 30 consecutive days apart. Oral hypoglycaemic treatment ≥30 consecutive days. Insulin ≥30 consecutive days. HgbA1c ≥6.5% (according to American Diabetes Association - ADA) Symptoms of Diabetes and Random Plasma Glucose (RPG) ≥ 11.1 mmol/L. 2-hour Plasma Glucose (2-hPG) ≥ 11.1 mmol/L during an oral glucose tolerance test (OGTT). Baseline OGTT will be performed pre-transplant.

  28. Post Transplantation Diabetes Mellitus

    Time frame: 36 months

    The cumulative incidence of Post Transplantation Diabetes Mellitus (PTDM) after transplantation as defined below -Cumulative incidence of:

    ≥2 Fasting Plasma Glucose (FPG) ≥7,0 mmol/L ≥ 30 consecutive days apart. Oral hypoglycaemic treatment ≥30 consecutive days. Insulin ≥30 consecutive days. HgbA1c ≥6.5% (according to American Diabetes Association - ADA)Symptoms of Diabetes and Random Plasma Glucose (RPG) ≥ 11.1 mmol/L.

    2-hour Plasma Glucose (2-hPG) ≥ 11.1 mmol/L during an oral glucose tolerance test (OGTT). Baseline OGTT will be performed pre-transplant.

  29. Antidiabetic medication

    Time frame: 6 months

    Use of antidiabetic medication

  30. Antidiabetic medication

    Time frame: 12 months

    Use of antidiabetic medication

  31. Antidiabetic medication

    Time frame: 24 months

    Use of antidiabetic medication

  32. Antidiabetic medication

    Time frame: 36 months

    Use of antidiabetic medication

  33. Antihypertensive and lipid lowering drugs

    Time frame: 12 months

    Incidence and number of antihypertensive and lipid lowering drug

  34. Antihypertensive and lipid lowering drugs

    Time frame: 24 months

    Incidence and number of antihypertensive and lipid lowering drug

  35. Antihypertensive and lipid lowering drugs

    Time frame: 36 months

    Incidence and number of antihypertensive and lipid lowering drug

  36. Proteinuria

    Time frame: 12 months

    Development and magnitude of proteinuria

  37. Proteinuria

    Time frame: 24 months

    Development and magnitude of proteinuria

  38. Proteinuria

    Time frame: 36 months

    Development and magnitude of proteinuria

  39. Lipid profile

    Time frame: 12 months

    Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c)

  40. Lipid profile

    Time frame: 24 months

    Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c)

  41. Lipid profile

    Time frame: 36 months

    Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c)

  42. Cytomegalovirus

    Time frame: 0-36 months

    Incidence of Cytomegalovirus (CMV) that required treatment (CMV-infection and CMV syndrome).

  43. Malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers.

    Time frame: 36 months

    Cumulative incidence of malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers.

  44. Safety and tolerability

    Time frame: 0-36 months

    Safety and tolerability

  45. Quality of life assessed by EQ5D Questionnaire

    Time frame: 12 months

    Quality of life, the relative difference over time will be investigated after LTx, where 5 questions are raised and answer is between 11111 (no problems) and 33333 (extreme problems in all dimensions)

  46. Quality of life assessed by St Georges Respiratory Questionnaire (SGRQ)

    Time frame: 12 months

    Quality of life, the relative difference over time will be investigated after LTx. The SGRQ total score ranges from 0 to 100 where 100 indicates the worst quality of life.

  47. Quality of life, assessed by EQ5D Questionnaire

    Time frame: 24 months

    Quality of life, the relative difference over time will be investigated after LTx, where 5 questions are raised and answer is between 11111 (no problems) and 33333 (extreme problems in all dimensions).

  48. Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ)

    Time frame: 24 months

    Quality of life, the relative difference over time will be investigated after LTx. The SGRQ total score ranges from 0 to 100 where 100 indicates the worst quality of life.

  49. Quality of life, assessed by EQ5D Questionnaire (SGRQ)

    Time frame: 36 months

    Quality of life, the relative difference over time will be investigated after LTx, where 5 questions are raised and answer is between 11111 (no problems) and 33333 (extreme problems in all dimensions).

  50. Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ)

    Time frame: 36 months

    Quality of life, the relative difference over time will be investigated after LTx. The SGRQ total score ranges from 0 to 100 where 100 indicates the worst quality of life.

  51. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 0h after administration, of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  52. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 1h after administration of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  53. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 2h after administration of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  54. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 3h after administration of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  55. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 4h after administration of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  56. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 6h after administration of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  57. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics (from whole blood concentrations from at 8h after administration and of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  58. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics (from whole blood concentrations from at 10h after administration and of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  59. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics (from whole blood concentrations at 12h after administration and of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  60. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 23h after administration and of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  61. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics from whole blood concentrations at 24h after administration and of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  62. Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population

    Time frame: week 4

    Define the pharmacokinetics as an AUC construction, of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  63. Pharmacokinetics of the Tacrolimus drug in patients in the CF sub group

    Time frame: 6 months

    Define the pharmacokinetics as an AUC construction, of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.

  64. Immunological equipotency of tacrolimus and cyclosporine A

    Time frame: 0-36 months

    Immunological equipotency of tacrolimus once daily (OD) and cyclosporine A twice daily (BiD) in vivo and in vitro, according to separate protocol.

  65. Occurrence of treatment failures

    Time frame: 0-36 months

    Occurrence of treatment failures up to or at 36 months; defined as a composite endpoint of graft loss, death, loss to follow up or discontinuation due to lack of efficacy or toxicity (at least one condition must be present).

  66. Recovery of right heart function

    Time frame: 0-36 months

    Recovery of right heart function irrespective of diagnosis in patients with pulmonary arterial hypertension (PAH, categories 1-5 according to WHO 1-5).

Sponsors and collaborators

Lead sponsor

Vastra Gotaland Region

Other Gov

Collaborators

  • Copenhagen University Hospital, Denmark
  • Helsinki University Central Hospital
  • Oslo University Hospital
  • Skane University Hospital

Registry information

Official study 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

Acronym: ScanCLAD

Important dates

Study start
2016
Primary completion
2025
Study completion
2026
First posted
Oct 18, 2016
Registry last updated
Apr 26, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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