Lung Transplant
Conditions
Brief summary
Patients undergoing a lung transplant will be enrolled. All patients will undergo lung transplantation with standard post-operative management, including triple immunosuppression. As soon as the patient is deemed appropriate to take medications via the oral route, they will be converted from IR tacrolimus to Envarsus XR. Patients will be followed per site's standard of care.
Detailed description
Lung transplantation will be performed per standard-of-care techniques. All post-transplant management, including initial triple immunosuppression, will be carried out per standard of care. Once the patient is able to take medications via the oral route, they will be converted to Envarsus XR, which will be maintained for the first year post-lung transplant.
Interventions
Envarsus XR is an FDA-approved drug for the prophylaxis of organ rejection in de novo kidney transplant patients or in kidney transplant patients converted from IR tacrolimus when used with other immunosuppressants. Envarsus XR is a novel extended-release formulation of tacrolimus created using MeltDose technology. Envarsus XR is available in tablet form. It is available in 0.75, 1, and 4 mg tablets.
Historical cohort of 20 subjects who will be maintained on IR tacrolimus following transplant. Dosing will be converted on an individual basis (Capsules: 0.5 mg, 1 mg and 5 mg or Injection: 5 mg) . All patients will be initiated on IR tacrolimus either under the tongue (sublingual) or as a solution given through a tube placed through the nose into the stomach, which is standard of care for all lung transplant recipients.
Sponsors
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Prospective arm: * Age ≥ 18 years * Received a lung transplant at NYU Langone Health * Be able to convert to Envarsus XR within the first month post-transplant * Able and willing to provide informed consent Historical control: * Age ≥ 18 years * Received a lung transplant at NYU Langone Health * Completed one year from transplant on IR tacrolimus
Exclusion criteria
Prospective arm: * Contraindication to tacrolimus due to allergic or adverse reactions * Pregnant or nursing women * Multi-organ transplant recipient Historical control: * Contraindication to tacrolimus due to allergic or adverse reactions (not including chronic kidney disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Remaining on Envarsus XR at 1 Year | 1 Year Post-Transplant | The primary endpoint is the percentage of patients remaining on Envarsus XR at the 1-year follow-up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Rejection Standardized Score (CRSS) | 1 Year Post-Transplant | The CRSS is a novel measure of burden of ACR. The score ranges from 0-6; higher scores indicate greater severity of burden of ACR. |
| Number of Treated Episodes of ACR | Up to 1 Year Post-Transplant | Number of participants with treated episodes of biopsy-proven or clinically suspected rejection requiring treatment with intravenous methylprednisolone or anti-thymocyte globulin. |
| Number of Participants With of Chronic Lung Allograft Dysfunction (CLAD) | Up to 1 Year Post-Transplant | Number of participants with at least 1 instance of CLAD. |
| Freedom From Acute Cellular Rejection (ACR) at 1 Year | Up to 1 Year Post-Transplant | Number of participants who did not experience ACR as of the 1-year follow-up. |
| Change in Estimated Glomerular Filtration Rate (eGFR) | Baseline, 1 Year Post-Transplant | Change in Estimated Glomerular Filtration Rate (eGFR) at 1 year post-transplant from pre-transplant. |
| Overall Survival at 1 Year | 1 Year Post-Transplant | The percentage of participants who are alive at 1 year post-transplant. |
| Number of Participants With De Novo Donor-Specific Antibody (DSA) | Up to 1 Year Post-Transplant | Number of individuals in whom an antibody is detected after transplantation. |
Countries
United States
Participant flow
Pre-assignment details
41 individuals were enrolled to participate in the trial; 1 individual did not begin treatment in the study, thus, only 40 participants started the study. Data on 24 historical control individuals were collected and analyzed retrospectively for the secondary outcome measures, but these 24 individuals were not recruited nor enrolled into the study, thus, they are not reflected in the total Protocol Enrollment figure.
Participants by arm
| Arm | Count |
|---|---|
| Envarsus XR Envarsus XR to be initiated once patient is tolerating oral medications
Extended-Release Tacrolimus: Envarsus XR is an FDA-approved drug for the prophylaxis of organ rejection in de novo kidney transplant patients or in kidney transplant patients converted from IR tacrolimus when used with other immunosuppressants. Envarsus XR is a novel extended-release formulation of tacrolimus created using MeltDose technology. Envarsus XR is available in tablet form. It is available in 0.75, 1, and 4 mg tablets. | 40 |
| IR Tacrolimus (Historical Control) Historical cohort of patients maintained on IR tacrolimus following transplant
Immediate-Release Tacrolimus: Historical cohort of 20 subjects who will be maintained on IR tacrolimus following transplant. Dosing will be converted on an individual basis (Capsules: 0.5 mg, 1 mg and 5 mg or Injection: 5 mg) . All patients will be initiated on IR tacrolimus either under the tongue (sublingual) or as a solution given through a tube placed through the nose into the stomach, which is standard of care for all lung transplant recipients. | 24 |
| Total | 64 |
Baseline characteristics
| Characteristic | Envarsus XR | Total | IR Tacrolimus (Historical Control) |
|---|---|---|---|
| Age, Continuous | 59 years | 60.75 years | 62.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 25 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 39 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 10 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 25 Participants | 7 Participants |
| Race (NIH/OMB) White | 13 Participants | 26 Participants | 13 Participants |
| Region of Enrollment United States | 40 participants | 64 participants | 24 participants |
| Sex: Female, Male Female | 15 Participants | 23 Participants | 8 Participants |
| Sex: Female, Male Male | 25 Participants | 41 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 24 |
| other Total, other adverse events | 29 / 40 | 0 / 0 |
| serious Total, serious adverse events | 1 / 40 | 0 / 0 |
Outcome results
Primary
Percentage of Patients Remaining on Envarsus XR at 1 Year
The primary endpoint is the percentage of patients remaining on Envarsus XR at the 1-year follow-up visit.
Time frame: 1 Year Post-Transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Envarsus XR | Percentage of Patients Remaining on Envarsus XR at 1 Year | 40 Participants |
Secondary
Change in Estimated Glomerular Filtration Rate (eGFR)
Change in Estimated Glomerular Filtration Rate (eGFR) at 1 year post-transplant from pre-transplant.
Time frame: Baseline, 1 Year Post-Transplant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Envarsus XR | Change in Estimated Glomerular Filtration Rate (eGFR) | -56.2 mL/min/1.73m2 | Standard Deviation 27.1 |
| IR Tacrolimus (Historical Control) | Change in Estimated Glomerular Filtration Rate (eGFR) | -40.3 mL/min/1.73m2 | Standard Deviation 21.2 |
Secondary
Composite Rejection Standardized Score (CRSS)
The CRSS is a novel measure of burden of ACR. The score ranges from 0-6; higher scores indicate greater severity of burden of ACR.
Time frame: 1 Year Post-Transplant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Envarsus XR | Composite Rejection Standardized Score (CRSS) | 0.19 score on a scale | Standard Deviation 0.37 |
| IR Tacrolimus (Historical Control) | Composite Rejection Standardized Score (CRSS) | 0.33 score on a scale | Standard Deviation 0.43 |
Secondary
Freedom From Acute Cellular Rejection (ACR) at 1 Year
Number of participants who did not experience ACR as of the 1-year follow-up.
Time frame: Up to 1 Year Post-Transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Envarsus XR | Freedom From Acute Cellular Rejection (ACR) at 1 Year | 5 Participants |
| IR Tacrolimus (Historical Control) | Freedom From Acute Cellular Rejection (ACR) at 1 Year | 6 Participants |
Secondary
Number of Participants With De Novo Donor-Specific Antibody (DSA)
Number of individuals in whom an antibody is detected after transplantation.
Time frame: Up to 1 Year Post-Transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Envarsus XR | Number of Participants With De Novo Donor-Specific Antibody (DSA) | 19 Participants |
| IR Tacrolimus (Historical Control) | Number of Participants With De Novo Donor-Specific Antibody (DSA) | 4 Participants |
Secondary
Number of Participants With of Chronic Lung Allograft Dysfunction (CLAD)
Number of participants with at least 1 instance of CLAD.
Time frame: Up to 1 Year Post-Transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Envarsus XR | Number of Participants With of Chronic Lung Allograft Dysfunction (CLAD) | 0 Participants |
| IR Tacrolimus (Historical Control) | Number of Participants With of Chronic Lung Allograft Dysfunction (CLAD) | 0 Participants |
Secondary
Number of Treated Episodes of ACR
Number of participants with treated episodes of biopsy-proven or clinically suspected rejection requiring treatment with intravenous methylprednisolone or anti-thymocyte globulin.
Time frame: Up to 1 Year Post-Transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Envarsus XR | Number of Treated Episodes of ACR | 8 Participants |
| IR Tacrolimus (Historical Control) | Number of Treated Episodes of ACR | 6 Participants |
Secondary
Overall Survival at 1 Year
The percentage of participants who are alive at 1 year post-transplant.
Time frame: 1 Year Post-Transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Envarsus XR | Overall Survival at 1 Year | 100 Percentage of participants |
| IR Tacrolimus (Historical Control) | Overall Survival at 1 Year | 100 Percentage of participants |