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

NCT02936505 | Active Not Recruiting DMC

• 9 other identifiers: Version 8.0154-162015-004137-27T-798-16 (amendement)T002-17 (amendement)T 055-18 (amendement)T568-18 (amendement)2019-06057 (amendement)2021-05380-02 (amendement)
• Study Type: interventional
• Target: 249
• Locations: 4 countries
• Sites: 5

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.

Conditions

Lung Transplantation; Allografts

Keywords

chronic lung allograft dysfunction; cyclosporin; tacrolimus; Bronchiolitis Obliterans Syndrome; Restrictive Allograft Syndrome; CLAD; immunization; renal function; survival

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (66)

• Glomerular Filtration Rate

  3 months

• Primary graft dysfunction

  72 hours

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

  12 months

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

  24 months

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

  36 months

Study Arms (2)

Arm A:Cyclosporine

ACTIVE COMPARATOR

Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label.

Drug: Cyclosporine; Drug: Mycophenolate mofetil (MMF); Drug: Rabbit Anti thymocyte globulin; Drug: Corticosteroids

Arm B:Tacrolimus

EXPERIMENTAL

Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids.

Drug: Mycophenolate mofetil (MMF); Drug: Rabbit Anti thymocyte globulin; Drug: Corticosteroids; Drug: Tacrolimus

Interventions

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.

Also known as: Sandimmun Neural

Arm A:Cyclosporine

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.

Also known as: Cellcept

Arm A:Cyclosporine; Arm B:Tacrolimus

Rabbit Anti thymocyte globulin DRUG

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

Also known as: Thymoglobulin®

Arm A:Cyclosporine; Arm B:Tacrolimus

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.

Also known as: Methylprednisolon

Arm A:Cyclosporine; Arm B:Tacrolimus

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.

Also known as: Advagraf®

Arm B:Tacrolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Oslo University Hospital: collaborator
• Helsinki University Central Hospital: collaborator
• Skane University Hospital: collaborator
• Copenhagen University Hospital, Denmark: collaborator

Study Sites (5)

Rigshospitalet

Copenhagen, Denmark

Location

Helsinki University Hospital

Helsinki, Finland

Location

Oslo University Hospital

Oslo, Norway

Location

Sahlgrenska Univ Hospital

Gothenburg, Sweden

Location

Skåne University Hospital

Lund, Sweden

Location

Related Publications (2)

• 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.

  PMID: 31993943 BACKGROUND

• 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.

  PMID: 37703908 DERIVED

Related Links

• Design manuscript

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Cyclosporine; Mycophenolic Acid; Antilymphocyte Serum; thymoglobulin; Adrenal Cortex Hormones; Methylprednisolone; Tacrolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Macrolides; Lactones

Study Officials

• Göran Dellgren, MD, PhD

  Sahlgrenska Univ Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: October 15, 2016
• First Posted: October 18, 2016
• Study Start: October 12, 2016
• Primary Completion: October 30, 2025
• Study Completion (Estimated): October 30, 2026
• Last Updated: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); DK (1); FI (1); NO (1)