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

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

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 Overview

• Status: Active, not recruiting
• Conditions: Lung Transplantation; Allografts
• Intervention / Treatment: Drug: Cyclosporine; Drug: Mycophenolate mofetil (MMF); Drug: Rabbit Anti thymocyte globulin; Drug: Corticosteroids; Drug: Tacrolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• Sweden
  • Göteborg, Sweden
    • Sahlgrenska Univ Hospital
  • Lund, Sweden
    • Skane University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A:Cyclosporine; Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label.	Drug: Cyclosporine; 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; Drug: Mycophenolate mofetil (MMF); 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; Drug: Rabbit Anti thymocyte globulin; Induction therapy: Thymoglobulin® (Rabbit Anti thymocyte globulin)(1.5 mg/kg given immediately postoperatively).; Other Names: Thymoglobulin®; Drug: Corticosteroids; 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
Experimental: Arm B:Tacrolimus; Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids.	Drug: Mycophenolate mofetil (MMF); 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; Drug: Rabbit Anti thymocyte globulin; Induction therapy: Thymoglobulin® (Rabbit Anti thymocyte globulin)(1.5 mg/kg given immediately postoperatively).; Other Names: Thymoglobulin®; Drug: Corticosteroids; 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; Drug: Tacrolimus; 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	72 hours
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
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
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
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

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Oslo University Hospital; Helsinki University Central Hospital; Skane University Hospital; Copenhagen University Hospital, Denmark
• Investigators: Study Chair: Göran Dellgren, MD, PhD, Sahlgrenska Univ Hospital

Publications and helpful links

General Publications

• 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.

Helpful Links

• Design manuscript

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2016
• Primary Completion (Anticipated): October 30, 2025
• Study Completion (Anticipated): October 30, 2026

Study Registration Dates

• First Submitted: October 15, 2016
• First Submitted That Met QC Criteria: October 17, 2016
• First Posted (Estimate): October 18, 2016

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: survival; renal function; tacrolimus; immunization; Bronchiolitis Obliterans Syndrome; chronic lung allograft dysfunction; cyclosporin; Restrictive Allograft Syndrome; CLAD
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Thymoglobulin; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• Other Study ID Numbers: Version 8.0; 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)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No