Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01429844




Trial ID
NCT01429844
Ethics application status
Date submitted
5/09/2011
Date registered
6/09/2011
Date last updated
6/09/2011

Titles & IDs
Public title
Tacrolimus Versus Cyclosporine for Immunosuppression After Lung Transplantation
Scientific title
Randomized, Open-label, Multi-Center Study Comparing Tacrolimus With Cyclosporin, Both Arms in Combination With Mycophenolate Mofetil and Corticosteroids for Prevention of Bronchiolitis Obliterans Syndrome in Lung Transplant Patients
Secondary ID [1] 0 0
EAILTx Tac vs. CsA in LuTx
Universal Trial Number (UTN)
Trial acronym
EAILTX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchiolitis Obliterans 0 0
Immunosuppression 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tacrolimus
Treatment: Drugs - Cyclosporine

Active Comparator: Tacrolimus - Tacrolimus in combination with mycophenolate mofetil and steroids for denovo immunosuppression after lung transplantation

Active Comparator: Cyclosporine - Cyclopsorine in combination with mycophenolate mofetil and steroids for denovo immunosuppression after lung transplantation


Treatment: Drugs: Tacrolimus
Tacrolimus therapy was started immediately after transplantation with a continuous intravenous infusion of 0.01-0.03 mg/kg/d. After extubation, the mode of delivery was switched to oral administration (b.i.d.) with doses of 0.05-0.3 mg/kg/d. Tacrolimus doses were adjusted to trough levels. Target C0 (trough) levels were 10-15 ng/ml for the first 3 months after transplantation and 8-12 ng/ml thereafter with dose adjustments according to patient outcome.

Treatment: Drugs: Cyclosporine
Cyclosporine therapy was started immediately after transplantation with a continuous intravenous infusion of 1-3 mg/kg/d. After extubation the mode of delivery was switched to oral administration (b.i.d. or t.i.d.) with doses of 4-18 mg/kg/d. Cyclosporine doses were adjusted to C0 or C2 levels according to local practice. Target trough levels were 200 - 300 ng/ml for the first 3 months after transplantation and 150 - 200 ng/ml thereafter.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of bronchiolitis obliterans syndrome - The incidence of patients with bronchiolitis obliterans syndrome (BOS), defined as a sustained fall (for >1 month) in maximum FEV1 of 20% or more (compared to baseline) over three years post transplant.
Timepoint [1] 0 0
3 years post transplant
Secondary outcome [1] 0 0
Acute allograft rejection - One- and 3-year rates of acute allograft rejection determined by clinical criteria or transbronchial lung biopsy.
Timepoint [1] 0 0
3 years post transplant
Secondary outcome [2] 0 0
Patient and graft survival - Patient and graft survival at one and three years
Timepoint [2] 0 0
3 years post transplant
Secondary outcome [3] 0 0
Incidence and spectrum of infections - Incidence and spectrum (viral, bacterial, fungal)of infections after transplantation
Timepoint [3] 0 0
3 years post transplant
Secondary outcome [4] 0 0
Renal failure - Post operative onset of renal dysfunction (defined as a persistent increase in serum creatinine of > 2mg/dl) or dialysis dependency
Timepoint [4] 0 0
3 years post transplant
Secondary outcome [5] 0 0
Treatment failure - Treatment failure defined as drug discontinuation (e.g. conversion to a different immunosuppression regimen)
Timepoint [5] 0 0
3 years post transplant

Eligibility
Key inclusion criteria
- male or female recipients of a first heart-lung

- bilateral or single lung allograft suitable to receive triple immunosuppressive
therapy with tacrolimus or cyclosporine, MMF and corticosteroids per standard
guidelines

- Age range = 18-66 years

- Able to understand the purposes and risks of the study

- Female patients of child bearing age agreeing to maintain effective birth control
practice during the follow-up period
Minimum age
18 Years
Maximum age
66 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- need for immunosuppressive regimen other than study medication or received additional
organ transplantations

- Pregnant women, nursing mothers or women unwilling to use adequate contraception

- Serologic evidence of human immunodeficiency virus, hepatitis B surface antigen or
hepatitis C virus antibodies

- Panresistant infections with Burkholderia cepacia or mycobacteria during the last 12
months preceding lung transplantation

- Patients with renal insufficiency (creatinine clearance < 40 ml/min

- Patients in need of invasive ventilator devices or extracorporeal membrane oxygenation

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
NSW 2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Wien
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Germany
State/province [4] 0 0
Essen
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Germany
State/province [6] 0 0
Jena
Country [7] 0 0
Germany
State/province [7] 0 0
Kiel
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Cordoba
Country [10] 0 0
Spain
State/province [10] 0 0
La Coruna
Country [11] 0 0
Spain
State/province [11] 0 0
Madrid
Country [12] 0 0
Spain
State/province [12] 0 0
Santander
Country [13] 0 0
Switzerland
State/province [13] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Universitätsklinikum Hamburg-Eppendorf
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to compare efficacy and safety of two different immunosuppressive
regimens for prevention of bronchiolitis obliterans syndrome (BOS) (chronic lung allograft
rejection)after lung transplantation: tacrolimus versus cyclosporine, both in combination
with mycophenolate mofetil and steroids. The study was powered to detect a 15% reduction in
BOS in tacrolimus treated patients.

Study design: open-label, randomized, comparative, multi-center, investigator driven
Trial website
https://clinicaltrials.gov/show/NCT01429844
Trial related presentations / publications
Aurora P, Edwards LB, Kucheryavaya AY, Christie JD, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: thirteenth official pediatric lung and heart-lung transplantation report--2010. J Heart Lung Transplant. 2010 Oct;29(10):1129-41. doi: 10.1016/j.healun.2010.08.008.
Reichenspurner H, Girgis RE, Robbins RC, Conte JV, Nair RV, Valentine V, Berry GJ, Morris RE, Theodore J, Reitz BA. Obliterative bronchiolitis after lung and heart-lung transplantation. Ann Thorac Surg. 1995 Dec;60(6):1845-53. Review.
Snell GI, Boehler A, Glanville AR, McNeil K, Scott JP, Studer SM, Wallwork J, Westall G, Zamora MR, Stewart S. Eleven years on: a clinical update of key areas of the 1996 lung allograft rejection working formulation. J Heart Lung Transplant. 2007 May;26(5):423-30. Review.
Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002 Mar;21(3):297-310. Review.
Hachem RR, Yusen RD, Chakinala MM, Meyers BF, Lynch JP, Aloush AA, Patterson GA, Trulock EP. A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation. J Heart Lung Transplant. 2007 Oct;26(10):1012-8.
Keenan RJ, Konishi H, Kawai A, Paradis IL, Nunley DR, Iacono AT, Hardesty RL, Weyant RJ, Griffith BP. Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg. 1995 Sep;60(3):580-4; discussion 584-5.
Treede H, Klepetko W, Reichenspurner H, Zuckermann A, Meiser B, Birsan T, Wisser W, Reichert B; Munich and Vienna Lung Transplant Group. Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols. J Heart Lung Transplant. 2001 May;20(5):511-7.
Zuckermann A, Reichenspurner H, Birsan T, Treede H, Deviatko E, Reichart B, Klepetko W. Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial. J Thorac Cardiovasc Surg. 2003 Apr;125(4):891-900.
Sarahrudi K, Estenne M, Corris P, Niedermayer J, Knoop C, Glanville A, Chaparro C, Verleden G, Gerbase MW, Venuta F, Böttcher H, Aubert JD, Levvey B, Reichenspurner H, Auterith A, Klepetko W. International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection. J Thorac Cardiovasc Surg. 2004 Apr;127(4):1126-32.
Vitulo P, Oggionni T, Cascina A, Arbustini E, D'Armini AM, Rinaldi M, Meloni F, Rossi A, Viganò M. Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation. J Heart Lung Transplant. 2002 Apr;21(4):435-9.
McNeil K, Glanville AR, Wahlers T, Knoop C, Speich R, Mamelok RD, Maurer J, Ives J, Corris PA. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation. 2006 Apr 15;81(7):998-1003.
Orens JB, Estenne M, Arcasoy S, Conte JV, Corris P, Egan JJ, Egan T, Keshavjee S, Knoop C, Kotloff R, Martinez FJ, Nathan S, Palmer S, Patterson A, Singer L, Snell G, Studer S, Vachiery JL, Glanville AR; Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006 Jul;25(7):745-55.
Shyu S, Dew MA, Pilewski JM, DeVito Dabbs AJ, Zaldonis DB, Studer SM, Crespo MM, Toyoda Y, Bermudez CA, McCurry KR. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant. 2011 Jul;30(7):743-54. doi: 10.1016/j.healun.2011.01.714. Epub 2011 Mar 21.
Public notes

Contacts
Principal investigator
Name 0 0
Hermann Reichenspurner, MD, PhD
Address 0 0
Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries