Trial Outcomes & Findings for Tacrolimus Adjustment by NFAT-related Gene Expression in Lung Allograft Recipients. (NCT NCT02278952)
NCT ID: NCT02278952
Last Updated: 2019-12-03
Results Overview
The prescribed tacrolimus dosage was determined by the treating physician who was not aware of the study-assay values. For the study assay, two blood draws were collected at a study visit during the assessment period (from 1 month up to 18 months post-transplant). The first draw occurred before tacrolimus dosage (trough) and the second occurred 90 to 120 minutes after tacrolimus dosage (peak). To determine MRE, whole blood was stimulated, RNA was extracted, and residual expression of NFAT-related cytokines (NFAT: nuclear factor of activated T-cells) was determined by quantitative polymerase chain reaction (qPCR). Researchers stratified blood draws based on subject's rejection pathology at time of blood draw and observed percentage distribution of MRE values within each rejection pathology group. Observed differences between MRE distributions within non-rejection group and rejection groups.
COMPLETED
50 participants
from 1 month up to 18 months post-transplant
2019-12-03
Participant Flow
Lung transplant recipients treated at UCSF with tacrolimus-based immunosuppressive regimen recruited one to two months post-transplant.
Participants followed for 6 to 18 months post transplantation. Study visits performed within one day of a clinical bronchoscopy scheduled either for cause, such as suspected infection or rejection, or for surveillance at 2, 3, 6, 12, or 18 months.
Unit of analysis: Biopsies
Participant milestones
| Measure |
Lung Transplant Participants
Lung transplant participants treated at UCSF with tacrolimus-based immunosuppression were followed until 18 months post-transplant, or until the participant's death or withdrawal.
|
|---|---|
|
Overall Study
STARTED
|
50 225
|
|
Overall Study
COMPLETED
|
44 117
|
|
Overall Study
NOT COMPLETED
|
6 108
|
Reasons for withdrawal
| Measure |
Lung Transplant Participants
Lung transplant participants treated at UCSF with tacrolimus-based immunosuppression were followed until 18 months post-transplant, or until the participant's death or withdrawal.
|
|---|---|
|
Overall Study
Insufficient Sample
|
6
|
Baseline Characteristics
Tacrolimus Adjustment by NFAT-related Gene Expression in Lung Allograft Recipients.
Baseline characteristics by cohort
| Measure |
Lung Transplant Participants
n=44 Participants
Lung transplant participants treated at UCSF with tacrolimus-based immunosuppression were followed until 18 months post-transplant, or until the participant's death or withdrawal.
|
|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 11 • n=39 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
|
Lung Disease Diagnosis Group
A-Obstructive
|
8 Participants
n=39 Participants
|
|
Lung Disease Diagnosis Group
B-Pulmonary vascular
|
1 Participants
n=39 Participants
|
|
Lung Disease Diagnosis Group
C-Cystic Fibrosis
|
2 Participants
n=39 Participants
|
|
Lung Disease Diagnosis Group
D-Restrictive
|
33 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: from 1 month up to 18 months post-transplantPopulation: Number of participants' study visits analyzed determined by the availability and quality of samples at both time points.
The prescribed tacrolimus dosage was determined by the treating physician who was not aware of the study-assay values. For the study assay, two blood draws were collected at a study visit during the assessment period (from 1 month up to 18 months post-transplant). The first draw occurred before tacrolimus dosage (trough) and the second occurred 90 to 120 minutes after tacrolimus dosage (peak). To determine MRE, whole blood was stimulated, RNA was extracted, and residual expression of NFAT-related cytokines (NFAT: nuclear factor of activated T-cells) was determined by quantitative polymerase chain reaction (qPCR). Researchers stratified blood draws based on subject's rejection pathology at time of blood draw and observed percentage distribution of MRE values within each rejection pathology group. Observed differences between MRE distributions within non-rejection group and rejection groups.
Outcome measures
| Measure |
Non-rejection
n=106 biopsies
Blood draw samples collected at the time of bronchoscopy with biopsy. Samples included if both time points (before tacrolimus dose and 90 to 120 minutes after dose) were collected, samples provided good quality RNA, and the patient had no evidence of acute cellular rejection. Acute cellular rejection was determined based on clinical interpretation of transbronchial biopsy specimens and graded according to International Society of Heart and Lung Transplantation (ISHLT) guidelines, with non-rejection defined as "A0B0."
|
Rejection
n=11 biopsies
Transbronchial biopsy showing A\>0 or B\>0 pathology with no rejection defined as A = 0 in perivascular interstitial components of the lung and B = 0 in airway components of the lung.
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|---|---|---|
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Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Acute Cellular Rejection
|
39.5 percentage of mean residual expression
Standard Error 2.9
|
41.7 percentage of mean residual expression
Standard Error 6.9
|
PRIMARY outcome
Timeframe: from 1 month up to 18 months post-transplantPopulation: Number of participants' study visits
Researchers stratified blood draws based on subject's airway infection status at time of blood draw (based on biopsy results) and observed percentage distribution of MRE values within each infection status group. Researchers observed differences between MRE distributions within subjects with airway infection at time of blood draw and subjects with no infection diagnosis.
Outcome measures
| Measure |
Non-rejection
n=100 biopsies
Blood draw samples collected at the time of bronchoscopy with biopsy. Samples included if both time points (before tacrolimus dose and 90 to 120 minutes after dose) were collected, samples provided good quality RNA, and the patient had no evidence of acute cellular rejection. Acute cellular rejection was determined based on clinical interpretation of transbronchial biopsy specimens and graded according to International Society of Heart and Lung Transplantation (ISHLT) guidelines, with non-rejection defined as "A0B0."
|
Rejection
n=17 biopsies
Transbronchial biopsy showing A\>0 or B\>0 pathology with no rejection defined as A = 0 in perivascular interstitial components of the lung and B = 0 in airway components of the lung.
|
|---|---|---|
|
Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Infection
|
14.4 percentage of mean residual expression
Standard Deviation 2.9
|
22.2 percentage of mean residual expression
Standard Deviation 4.6
|
SECONDARY outcome
Timeframe: from 1 month (4 weeks) up to 18 months (82 weeks) post-transplantPopulation: Number of participants' study visits
Researchers observed percentage distribution of MRE values at time of blood draw from study visits at 4 weeks post-transplant up to 82 weeks post-transplant. Researchers observed association between percentage of MRE at time of blood draw and the number of weeks post-transplant.
Outcome measures
| Measure |
Non-rejection
n=117 biopsies
Blood draw samples collected at the time of bronchoscopy with biopsy. Samples included if both time points (before tacrolimus dose and 90 to 120 minutes after dose) were collected, samples provided good quality RNA, and the patient had no evidence of acute cellular rejection. Acute cellular rejection was determined based on clinical interpretation of transbronchial biopsy specimens and graded according to International Society of Heart and Lung Transplantation (ISHLT) guidelines, with non-rejection defined as "A0B0."
|
Rejection
Transbronchial biopsy showing A\>0 or B\>0 pathology with no rejection defined as A = 0 in perivascular interstitial components of the lung and B = 0 in airway components of the lung.
|
|---|---|---|
|
Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Weeks Post-Transplant
|
0.35 percentage of mean residual expression
Interval 0.04 to 0.66
|
—
|
SECONDARY outcome
Timeframe: from 1 month up to 18 months post-transplantPopulation: Number of participants' study visits
Researchers observed percentage distribution of MRE values on the day of blood draws. Researchers measured tacrolimus concentration in blood drawn before tacrolimus dosage (trough) and observed the association between percentage of MRE on the day of blood draw and tacrolimus trough level.
Outcome measures
| Measure |
Non-rejection
n=117 biopsies
Blood draw samples collected at the time of bronchoscopy with biopsy. Samples included if both time points (before tacrolimus dose and 90 to 120 minutes after dose) were collected, samples provided good quality RNA, and the patient had no evidence of acute cellular rejection. Acute cellular rejection was determined based on clinical interpretation of transbronchial biopsy specimens and graded according to International Society of Heart and Lung Transplantation (ISHLT) guidelines, with non-rejection defined as "A0B0."
|
Rejection
Transbronchial biopsy showing A\>0 or B\>0 pathology with no rejection defined as A = 0 in perivascular interstitial components of the lung and B = 0 in airway components of the lung.
|
|---|---|---|
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Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Tacrolimus Trough Level
|
-1.687 percentage of mean residual expression
Interval -3.714 to 0.397
|
—
|
SECONDARY outcome
Timeframe: from 1 month up to 18 months post-transplantPopulation: Number of participants' study visits
Researchers observed percentage distribution of MRE values on the day of blood draws and measured tacrolimus, prednisone, and mycophenolate dose at the time of blood draw. Researchers observed the association between percentage of MRE on the day of blood draw and tacrolimus, prednisone, and mycophenolate dose, respectively, at the time of blood draw.
Outcome measures
| Measure |
Non-rejection
n=117 biopsies
Blood draw samples collected at the time of bronchoscopy with biopsy. Samples included if both time points (before tacrolimus dose and 90 to 120 minutes after dose) were collected, samples provided good quality RNA, and the patient had no evidence of acute cellular rejection. Acute cellular rejection was determined based on clinical interpretation of transbronchial biopsy specimens and graded according to International Society of Heart and Lung Transplantation (ISHLT) guidelines, with non-rejection defined as "A0B0."
|
Rejection
Transbronchial biopsy showing A\>0 or B\>0 pathology with no rejection defined as A = 0 in perivascular interstitial components of the lung and B = 0 in airway components of the lung.
|
|---|---|---|
|
Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Medication Dosages
Tacrolimus dose
|
0.676 percentage of mean residual expression
Interval -1.159 to 2.511
|
—
|
|
Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Medication Dosages
Prednisone Dose
|
-1.687 percentage of mean residual expression
Interval -3.27 to -0.104
|
—
|
|
Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Medication Dosages
Mycophenolate Mofetil Dose
|
-0.0035 percentage of mean residual expression
Interval -0.013 to 0.006
|
—
|
Adverse Events
Lung Transplant Participants
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. John Greenland
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place