Viral Load Guided Immunosuppression After Lung Transplantation (VIGILung)

Philipps University Marburg

Status: Completed

Conditions: Transplantation Lung

Treatments: Other: Conventional tacrolimus dosing; Other: Tailored tacrolimus dosing

Study type: Interventional

Funder types: Other

Identifiers

NCT04198506

2019-001770-29 (EudraCT Number)

KKS-256

Details and patient eligibility

About

The VIGILung study is an open-label, randomized, multicenter trial in lung transplant recipients to investigate the safety and efficacy of personalized immunosuppression guided by DNA monitoring of Torque-Teno-Virus (TTV). The aim of the study is to investigate an individual adaptation of the calcineurin inhibitor tacrolimus (tailored calcineurin inhibitor dosing) by a non-invasive biomarker (TTV viral load in whole blood) compared to conventional calcineurin inhibitor dosing. Indicator for toxicity will be the glomerular filtration rate (GFR), which will be estimated using the CKD-EPI formula. 250 patients (age ≥ 18 years) with 21 to 42 days after de novo lung transplantation (bilateral or combined) will be screened as possible subjects eligible for the study. N = 144 patients have to be randomized in two study arms. In Arm 1 tacrolimus doses will be adapted according to the tacrolimus blood level (conventional therapeutic drug monitoring - TDM) and additionally depending on TTV viral load. In Arm 2 tacrolimus doses will be adapted according to TDM.

Enrollment: 146 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. patients 21 to 42 days after primary de novo lung transplantation (bilateral including combined)
2. age ≥ 18 years
3. tacrolimus based immunosuppression
4. written informed consent
5. detectable TTV load at randomization (>2,7 log 10)
6. negative serum pregnancy test in women of childbearing potential.
7. women of childbearing capacity must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence is not practiced, a combination of hormonal contraceptive (oral, injectable or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used.

Exclusion criteria

1. patients after unilateral or re-do lung transplantation
2. history or high-risk of obstructive airway complications after lung transplantation
3. respiratory failure (need for oxygen therapy or ventilation at screening after lung transplantation)
4. inability to undergo transbronchial biopsy
5. advanced kidney failure (GFR CKD-EPI <30 ml/min/1.73m2 at inclusion and/or current renal replacement therapy at inclusion or randomization
6. advanced liver cirrhosis (CHILD-Pugh Score C) after lung transplantation
7. fluctuating tacrolimus drug levels (less than 20% in target range after transplantation)
8. symptoms of significant mental illness and with inability to cooperate or communicate with the investigator.
9. unlikeliness to comply with the study requirements
10. HIV positivity
11. evidence of unsolved drug or alcohol addiction
12. breastfeeding women
13. simultaneous participation in other clinical trials if not permitted by the steering committee

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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146 participants in 2 patient groups

Tailored tacrolimus dosing

Experimental group

Description:

Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM) and additionally depending on TTV viral load.

Treatment:

Other: Tailored tacrolimus dosing

Conventional tacrolimus dosing

Active Comparator group

Description:

Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM).

Treatment:

Other: Conventional tacrolimus dosing