Viral Load Guided Immunosuppression After Lung Transplantation

Not Applicable

Completed

• Conditions: Transplantation Lung
• Interventions: Other: Tailored tacrolimus dosing; Other: Conventional tacrolimus dosing

• Registration Number: NCT04198506
• Lead Sponsor: Philipps University Marburg

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-05
• Study First Submitted QC: 2019-12-12
• Study First Posted: 2019-12-13
• Study Start: 2020-08-05
• Status Verified: 2025-03
• Primary Completion: 2025-03-07
• Study Completion: 2025-03-10
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
ΔGFR change of the glomerular filtration rate GFR	Between randomization and 12 months thereafter	The primary efficacy endpoint ΔGFR is defined as the change of the glomerular filtration rate GFR between randomization and 12 months thereafter. GFR will be estimated using the CKD-EPI formula.

Secondary Outcome Measures

Name	Time	Method
GFR (CKD-EPI)	1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization	Glomerular filtration rate (the Chronic Kidney Disease Epidemiology Collaboration - CKD-EPI) formula
GFR (Cystatin)	At randomization and 12 months after randomization	Glomerular filtration rate (Cystatin)
proportion of patients with biopsy-proven acute cellular rejection (grade A1 or higher)	Between randomization and 12 months after randomization	Proportion of patients with biopsy-proven acute cellular rejection (grade A1 or higher), between randomization and 12 months after randomization
proportion of patients with an episode of biopsy-proven lymphocytic bronchitis (grade B1R or higher)	Between randomization and 12 months after randomization	proportion of patients with an episode of biopsy-proven lymphocytic bronchitis (grade B1R or higher)
proportion of patients with cytomegalovirus (CMV)-infection and number of CMV-disease episodes	Between randomization and 12 months after randomization	proportion of patients with cytomegalovirus (CMV)-infection and number of CMV-disease
proportion of patients with community-acquired respiratory viral infection (CARV)	Between randomization and 12 months after randomization	proportion of patients with community-acquired respiratory viral infection (CARV)
proportion of patients with fungal and bacterial infections	Between randomization and 12 months after randomization	proportion of patients with fungal and bacterial infections
proportion of patients with any of the above mentioned infections	Between randomization and 12 months after randomization	proportion of patients with any of the above mentioned infections
proportion of patients with unscheduled or emergency hospitalizations	Between randomization and 12 months after randomization	proportion of patients with unscheduled or emergency hospitalizations
proportion of patients with ICU admissions	Between randomization and 12 months after randomization	proportion of patients with ICU admissions
quality of life (EQ-5D visual analog scale)	1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization	European Quality of Life 5 Dimensions - EQ-5D
proportion of patients with new or progressive malignancy	Between randomization and 12 months after randomization	proportion of patients with new or progressive malignancy
tacrolimus trough levels	1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization	tacrolimus trough levels
daily tacrolimus dose [mg]	1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization	daily tacrolimus dose \[mg\]
proportion of patients with increased/unchanged/decreased (compared to previous visit) target trough levels of tacrolimus	1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization	proportion of patients with increased/unchanged/decreased (compared to previous visit)
exercise capacity measured by the percent predicted distance achieved in the 6-minute walk test (6-MWT)	at randomization and 12 months thereafter	exercise capacity measured by the percent predicted distance achieved in the 6-minute walk test (6-MWT)
CD4-Lymphocytes counts	0, 6 and 12 months after randomization	CD4-Lymphocytes counts
proportion of patients with presence of donor specific antibodies	0, 6 and 12 months after randomization	proportion of patients with presence of donor specific antibodies
FEV1 in % baseline value	1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization	FEV1 in % baseline value
IgG-level	0, 6 and 12 months after randomization	IgG-level
incidence of chronic lung allograft dysfunction	Between randomization and 12 months thereafter	incidence of chronic lung allograft dysfunction
proportion of patients with rescue immunotherapy (defined by the use of ATG, Rituximab, Alemtuzumab, plasma exchange, immunoadsorption)	Between randomization and 12 months thereafter	proportion of patients with rescue immunotherapy (defined by the use of ATG, Rituximab, Alemtuzumab, plasma exchange, immunoadsorption)
time from randomization to graft loss (defined as re-do transplantation or death)	randomization until 12 months thereafter	time from randomization to graft loss (defined as re-do transplantation or death)

Trial Locations

Locations (2)

Medizinische Universität Wien, Klinische Abteilung für Thoraxchirurgie; 🇦🇹 Wien, Austria

Klinik für Pneumologie OE 6870, Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany