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| ID | Type | Description | Link |
|---|---|---|---|
| 154-16 | Other Identifier | EC, Gothenburg, Sweden | |
| 2015-004137-27 | EudraCT Number | ||
| T-798-16 (amendement) | Other Identifier | EC, Gothenburg, Sweden | |
| T002-17 (amendement) | Other Identifier | EC, Gothenburg, Sweden | |
| T 055-18 (amendement) | Other Identifier | EC, Gothenburg, Sweden | |
| T568-18 (amendement) | Other Identifier | EC, Gothenburg, Sweden | |
| 2019-06057 (amendement) | Other Identifier | EC (EPM), Gothenburg, Sweden | |
| 2021-05380-02 (amendement) | Other Identifier | EC (EPM), Gothenburg, Sweden |
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| Name | Class |
|---|---|
| Oslo University Hospital | OTHER |
| Helsinki University Central Hospital | OTHER |
| Skane University Hospital | OTHER |
| Copenhagen University Hospital, Denmark |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A:Cyclosporine | Active Comparator | Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label. |
|
| Arm B:Tacrolimus | Experimental | Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclosporine | Drug | Cyclosporin A (Sandimmun Neoral® or similar):
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with incidence of CLAD | The cumulative incidence of CLAD (including both BOS and RAS, as defined in the Appendix II) after lung transplantation. | 36 months is primary outcome |
| Number of patients with incidence of CLAD | The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 48 months after lung transplantation. | 48 months is outcome for the continuation study |
| Number of patients with incidence of CLAD | The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 60 months after lung transplantation. | 60 months is outcome for continuation study |
| Number of patients with incidence of CLAD | The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 72 months after lung transplantation. | 72 months is outcome for continuation study |
| Measure | Description | Time Frame |
|---|---|---|
| Glomerular Filtration Rate | Renal function evaluated by measured glomerular filtration rate | 3 months |
| Primary graft dysfunction | Cumulative incidence of primary graft dysfunction |
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Inclusion Criteria
Exclusion Criteria
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
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| Name | Affiliation | Role |
|---|---|---|
| Göran Dellgren, MD, PhD | Sahlgrenska Univ Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Copenhagen | Denmark | ||||
| Helsinki University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31993943 | Background | 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. | |
| 40118141 |
| Label | URL |
|---|---|
| Design manuscript | View source |
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Potentially this can be done, but needs to be according to GDPR. Figures with pulmonary function tests over time and related to CLAD are constructed in the study.
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| OTHER |
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|
|
| 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. |
|
|
| Rabbit Anti thymocyte globulin | Drug | Induction therapy: Thymoglobulin® (Rabbit Anti thymocyte globulin)(1.5 mg/kg given immediately postoperatively). |
|
|
| Corticosteroids | Drug | Corticosteroids:
|
|
|
| Tacrolimus | Drug |
|
|
|
| 72 hours |
| Composite measure of freedom from AR, CLAD, graft and patient survival | Composite measure of freedom from first event of AR, CLAD, graft survival, and patient survival | 12 months |
| Composite measure of freedom from AR, CLAD, graft and patient survival | Composite measure of freedom from first event of AR, CLAD, graft survival, and patient | 24 months |
| Composite measure of freedom from AR, CLAD, graft and patient survival | Composite measure of freedom from first event of AR, CLAD, graft survival, and patient | 36 months |
| Incidence of primary graft dysfunction | cumulative incidence of primary graft dysfunction | 72 hours |
| Patient survival | Patient survival | 1 year |
| Patient survival | Patient survival | 3 year |
| Cumulative incidence of acute allograft rejection and CLAD | 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. | 6 months |
| Cumulative incidence of acute allograft rejection and CLAD | 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. | 1 year |
| Cumulative incidence of acute allograft rejection and CLAD | 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. | 3 year |
| Cumulative incidence of BOS and RAS | The cumulative incidence of BOS and RAS | 6 months |
| Cumulative incidence of BOS and RAS | The cumulative incidence of BOS and RAS | 1 year |
| Cumulative incidence of BOS and RAS | The cumulative incidence of BOS and RAS | 3 year |
| Development of donor specific antibodies | Development of donor specific antibodies (DSA) according to specific protocol. | 12 months |
| Development of donor specific antibodies | Development of donor specific antibodies (DSA) according to specific protocol. | 24 months |
| Development of donor specific antibodies | Development of donor specific antibodies (DSA) according to specific protocol. | 36 months |
| Renal function mGFR | Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance. | 12 months |
| Renal function mGFR | Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance. | 24 months |
| Renal function mGFR | Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance. | 36 months |
| Renal function cGFR | Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas. | 3 months |
| Renal function cGFR | Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas. | 12 months |
| Renal function cGFR | Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas. | 24 months |
| Renal function cGFR | Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas. | 36 months |
| Post Transplantation Diabetes Mellitus | 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. | 6 months |
| Post Transplantation Diabetes Mellitus | 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. | 12 months |
| Post Transplantation Diabetes Mellitus | 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. | 24 months |
| Post Transplantation Diabetes Mellitus | 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. | 36 months |
| Antidiabetic medication | Use of antidiabetic medication | 6 months |
| Antidiabetic medication | Use of antidiabetic medication | 12 months |
| Antidiabetic medication | Use of antidiabetic medication | 24 months |
| Antidiabetic medication | Use of antidiabetic medication | 36 months |
| Antihypertensive and lipid lowering drugs | Incidence and number of antihypertensive and lipid lowering drug | 12 months |
| Antihypertensive and lipid lowering drugs | Incidence and number of antihypertensive and lipid lowering drug | 24 months |
| Antihypertensive and lipid lowering drugs | Incidence and number of antihypertensive and lipid lowering drug | 36 months |
| Proteinuria | Development and magnitude of proteinuria | 12 months |
| Proteinuria | Development and magnitude of proteinuria | 24 months |
| Proteinuria | Development and magnitude of proteinuria | 36 months |
| Lipid profile | Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c) | 12 months |
| Lipid profile | Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c) | 24 months |
| Lipid profile | Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c) | 36 months |
| Cytomegalovirus | Incidence of Cytomegalovirus (CMV) that required treatment (CMV-infection and CMV syndrome). | 0-36 months |
| Malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers. | Cumulative incidence of malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers. | 36 months |
| Safety and tolerability | Safety and tolerability | 0-36 months |
| Quality of life assessed by EQ5D Questionnaire | 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) | 12 months |
| Quality of life assessed by St Georges Respiratory Questionnaire (SGRQ) | 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. | 12 months |
| Quality of life, assessed by EQ5D Questionnaire | 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). | 24 months |
| Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ) | 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. | 24 months |
| Quality of life, assessed by EQ5D Questionnaire (SGRQ) | 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). | 36 months |
| Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ) | 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. | 36 months |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population | 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. | week 4 |
| Pharmacokinetics of the Tacrolimus drug in patients in the CF sub group | 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. | 6 months |
| Immunological equipotency of tacrolimus and cyclosporine A | Immunological equipotency of tacrolimus once daily (OD) and cyclosporine A twice daily (BiD) in vivo and in vitro, according to separate protocol. | 0-36 months |
| Occurrence of treatment failures | 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). | 0-36 months |
| Recovery of right heart function | Recovery of right heart function irrespective of diagnosis in patients with pulmonary arterial hypertension (PAH, categories 1-5 according to WHO 1-5). | 0-36 months |
| Helsinki |
| Finland |
| Oslo University Hospital | Oslo | Norway |
| Sahlgrenska Univ Hospital | Gothenburg | Sweden |
| Skåne University Hospital | Lund | Sweden |
| Derived |
| Joo S, Dhaygude K, Krebs R, Holmstrom E, Puhka M, Laitinen S, Dellgren G, Magnusson J, Holmberg EC, Svahn J, Lund TK, Leuckfeld I, Raivio P, Helantera I, Aberg F, Syrjala SO, Nykanen AI, Lemstrom KB. Extracellular vesicles in lung donor plasma: Potential indicators of donor organ quality. J Thorac Cardiovasc Surg. 2025 Sep;170(3):902-913. doi: 10.1016/j.jtcvs.2025.03.012. Epub 2025 Mar 19. |
| 37703908 | Derived | Dellgren G, Lund TK, Raivio P, Leuckfeld I, Svahn J, Holmberg EC, Olsen PS, Halme M, Fiane A, Lindstedt S, Riise GC, Magnusson J. Effect of once-per-day tacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial. Lancet Respir Med. 2024 Jan;12(1):34-44. doi: 10.1016/S2213-2600(23)00293-X. Epub 2023 Sep 10. |
| ID | Term |
|---|---|
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
| D001991 | Bronchitis |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D006086 | Graft vs Host Disease |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D009173 | Mycophenolic Acid |
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| D000305 | Adrenal Cortex Hormones |
| D008775 | Methylprednisolone |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |
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