Disorder Related to Lung TransplantationPhase 2NCT04415476
Standard Therapy Using Tacrolimus, Mycophenolate Mofetil and Prednisone For Chronic Lung Transplant Rejection (BOS)
A Phase 2 study testing Assigned Interventions in people with Disorder Related to Lung Transplantation and Chronic Rejection of Lung Transplant, run by University of Maryland, Baltimore.
Trial summary
This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs).To assess the efficacy and safety of sirolimus plus tacrolimus and prednisone (S) compared… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disorder Related to Lung Transplantation, Chronic Rejection of Lung Transplant, Decreased Immunologic Activity
- What is being tested?
- Assigned Interventions
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Jun 2020to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 18 or older.
- Recipient of a single or double pulmonary allograft at least twelve months before study entry.
- Clinically diagnosed BOS grade 1 or 2
- Receiving oral TAC-based immunosuppression according to institutional standards.
- Capable of understanding the purposes and risks of the study, has given written informed consent and agrees to comply with the study requirements and capable of protocol adherence.
- Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry.
- Stable to enable routine pre and post-transplant bronchoscopy with BAL and biopsy.
- Fasting cholesterol < 250 mg/dL, fasting triglycerides < 250 mg/dL -
Who cannot join
- Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry.
- Mechanical ventilation.
- At screening FEV1 < 1 liter and/or < FEV1 of 25 % predicted.
- Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy.
- Women who breastfeed.
- Known hypersensitivity to sirolimus.
Show all 15Show fewer
- Serum creatinine value of > 2.5 mg/dL or chronic dialysis use or liver disease with a bilirubin > 2 mg/dL.
- Subjects with severe underlying disease other than BOS that is thought to become fatal within four months of clinical assessment.
- Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to study entry. This is defined as any treatment that is implemented under an Investigational New Drug.
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
- Any co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the patient's participation in the clinical trial.
- Clinically significant bronchial strictures unresponsive to dilatation procedures.
- Subjects with malignancy diagnosed within one year prior to screen (with the exception of skin cancers).
- Lipid panel fasting cholesterol > 250 mg/dL, fasting triglycerides >250 mg/dL
- -
About this study
Official title: A Randomized, Open-label,Controlled Phase II b Study to Demonstrate Efficacy and Safety of Sirolimus Chronic Rejection After Lung Transplant
This is a prospective single-center, open-label, randomized, controlled pilot
study in the treatment of chronic rejection (CR), defined as grade 1 and 2
BOS, in adult recipients of a pulmonary allograft (single or double lungs).To assess the efficacy and safety of sirolimus plus tacrolimus and prednisone
(S) compared to standard therapy (tacrolimus, mycophenolate mofetil
(MMF) and prednisone) (ST) for chronic rejection, defined as grades 1 and 2
bronchiolitis obliterans syndrome (BOS); BOS defined as ≥ 20% decline
from maximal post-transplant FEV1.
Read the detailed description
This is a prospective single-center, open-label, randomized, controlled pilot
study in the treatment of chronic rejection (CR), defined as grade 1 and 2
BOS, in adult recipients of a pulmonary allograft (single or double lungs).
Patients meeting entry criteria shall demonstrate a sustained decline in FEV1
having met stage 1 or 2 BOS. Patients randomized to the study arm, will be
treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus
and prednisone compared to those patients randomized to defined ST alone
(tacrolimus, MMF and prednisone). The trial duration will be approximately
Primary endpoints will include:
Efficacy failure between ST and S randomized group investigational treatment regimens will be determined at 96 weeks after the last patient is randomization and enrolled at approximately study year 2. The control arm will receive standard of care treatment (ST) and immunosuppression according to the University of Maryland lung transplant protocol. Efficacy failure will be defined as the combined end point of progression of BOS (defined as at least a 20 % decline from the initial randomization FEV1 value confirmed by two separate measurements three weeks apart or more) or re-transplantation or death. The co-primary end point of FEV1 and FVC changes to define functional stabilization in the S arm compared to ST is to be completed when the last patient randomized (patient #30) has been enrolled for 2 years as well.
Efficacy of S is to be assessed using following parameters to determine its effect on lung function:
- Forced expiratory volume in one second (FEV1)
- Forced vital capacity (FVC)
- FEF 25-75
Secondary endpoints will include:
- General S tolerability
- Incidence and severity of adverse events (AE)
- Changes in clinical laboratory parameters from baseline after randomization
- Changes in vital signs
- Changes in physical examinations
- Incidence of infections
- Average maintenance doses of calcineurin inhibitors, antimetabolite agents, and corticosteroids
- Number of courses of augmented immunosuppressants
- Number and days of hospitalization
- Incidence of malignancies
- Overall mortality (including transplant-related mortality)
- Retransplantation
- Conditions
- Disorder Related to Lung Transplantation, Chronic Rejection of Lung Transplant, Decreased Immunologic Activity
- Being tested
- Assigned Interventions
- Keywords
- lung function, Lung Transplantation, case-control study, bronchiolitis obliterans syndrome (BOS)
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Assigned InterventionsDrug
Also called Tacrolimus, Mycophenolate mofetil, Prednisone, Sirolimus
This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs). Patients meeting entry criteria shall demonstrate a sustained decline in FEV1 having met stage 1 or 2 BOS. Patients randomized to the study arm, will be treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus and prednisone compared to those patients randomized to defined ST alone (tacrolimus, MMF and prednisone). The trial duration will be approximately 2 years for each subject randomized. Treatment compliance and safety will be monitored by clinic visits at 4-6 week intervals for the 2 year subject duration and will include standard physical examinations and monitoring of routine clinical and laboratory parameters including cause of hospitalizations and rate of adverse events including death in each group. T
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus and Tacrolimus and prednisone | Other | Assigned Interventions Sirolimus (Rapamune) Tacrolimus (Prograft) Prednisone (Deltasone, Prednicot, Rayos, Sterapred) Receives: Drug: Assigned Interventions |
| Standard of Care | Experimental | Arm1:) sirolimus and tacrolimus and prednisone group:
Tacrolimus, The patient will receive 0.1-0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 5-12 ng/ml.
Mycophenolate mofetil (NA )Stopped upon sirolimus initiation Sirolimus:1-5 mg/day PO if >40 kg / 1 mg/m²/day if <40 kg trough blood levels 5-12 ng/ml Prednisone:20 mg/day PO if >40 kg and 10 mg/day if <40 kg, adjust based on adverse effects.
Arm 2) Standard Therapy Tacrolimus:0.1 to 0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 8-12 ng/ml Mycophenolate mofetil:750-1250 mg bid PO and adjust to tolerance (WBCs and GI side effects Sirolimus: NA Prednisone: Prednisone dose 20 mg/day PO if >40 kg and 10 mg/day if <40 kg, adjust based on adverse effect Receives: Drug: Assigned Interventions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death
Increase in motility
Measured: 2 years
Re-Transplantation
Increase in re-transplantation from baseline
Measured: 2 years
FEV1 (Forced Respiratory Volume in 1 second)
Greater or equal to 20% decline in FEV1 from randomization
Measured: 2 years
Secondary outcomes (2)
FVC (Forced Vital Capacity)
Caparison between the two treatment groups.
Measured: 2 years
FEF (forced expiratory flow)
The rate of airflow recorded in measurements of forced vital capacity, usually calculated as an average flow over a given portion of the expiratory curve; the portion between 25 and 75 per cent of forced vital capacity.
Comparison on FEF(25-75) between the two treatment groups.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start30 Jun 2020 (estimated)
- Primary completion30 Jun 2024 (estimated)
- Study completion30 Jun 2028 (estimated)
Why it stopped: Study did not proceed to IRB approval.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Disorder Related to Lung TransplantationStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Paralled Assignment
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aldo T Iacono, MD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04415476
- Sponsor's protocol ID
- HP-00091412
- Status last verified
- Jun 2020
- First submitted
- 13 May 2020
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50. doi: 10.1056/NEJMoa043204.
PubMed 16407509
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label,Controlled Phase II b Study to Demonstrate Efficacy and Safety of Sirolimus Chronic Rejection After Lung Transplant
- ClinicalTrials.gov ID
- NCT04415476
- Acronym / sponsor ID
- HP-00091412
- Conditions
- Disorder Related to Lung Transplantation, Chronic Rejection of Lung Transplant, Decreased Immunologic Activity
- Keywords
- lung function, Lung Transplantation, case-control study, bronchiolitis obliterans syndrome (BOS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study did not proceed to IRB approval.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 30 Jun 2020 (estimated)
- Primary completion
- 30 Jun 2024 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 4 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective single-center, open-label, randomized, controlled pilot
study in the treatment of chronic rejection (CR), defined as grade 1 and 2
BOS, in adult recipients of a pulmonary allograft (single or double lungs).To assess the efficacy and safety of sirolimus plus tacrolimus and prednisone
(S) compared to standard therapy (tacrolimus, mycophenolate mofetil
(MMF) and prednisone) (ST) for chronic rejection, defined as grades 1 and 2
bronchiolitis obliterans syndrome (BOS); BOS defined as ≥ 20% decline
from maximal post-transplant FEV1.
Detailed description
This is a prospective single-center, open-label, randomized, controlled pilot
study in the treatment of chronic rejection (CR), defined as grade 1 and 2
BOS, in adult recipients of a pulmonary allograft (single or double lungs).
Patients meeting entry criteria shall demonstrate a sustained decline in FEV1
having met stage 1 or 2 BOS. Patients randomized to the study arm, will be
treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus
and prednisone compared to those patients randomized to defined ST alone
(tacrolimus, MMF and prednisone). The trial duration will be approximately
Primary endpoints will include:
Efficacy failure between ST and S randomized group investigational treatment regimens will be determined at 96 weeks after the last patient is randomization and enrolled at approximately study year 2. The control arm will receive standard of care treatment (ST) and immunosuppression according to the University of Maryland lung transplant protocol. Efficacy failure will be defined as the combined end point of progression of BOS (defined as at least a 20 % decline from the initial randomization FEV1 value confirmed by two separate measurements three weeks apart or more) or re-transplantation or death. The co-primary end point of FEV1 and FVC changes to define functional stabilization in the S arm compared to ST is to be completed when the last patient randomized (patient #30) has been enrolled for 2 years as well.
Efficacy of S is to be assessed using following parameters to determine its effect on lung function:
- Forced expiratory volume in one second (FEV1)
- Forced vital capacity (FVC)
- FEF 25-75
Secondary endpoints will include:
- General S tolerability
- Incidence and severity of adverse events (AE)
- Changes in clinical laboratory parameters from baseline after randomization
- Changes in vital signs
- Changes in physical examinations
- Incidence of infections
- Average maintenance doses of calcineurin inhibitors, antimetabolite agents, and corticosteroids
- Number of courses of augmented immunosuppressants
- Number and days of hospitalization
- Incidence of malignancies
- Overall mortality (including transplant-related mortality)
- Retransplantation
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Paralled Assignment
| Arm | Type | Receives |
|---|---|---|
| Sirolimus and Tacrolimus and prednisone | Other | Drug: Assigned InterventionsAssigned Interventions Sirolimus (Rapamune) Tacrolimus (Prograft) Prednisone (Deltasone, Prednicot, Rayos, Sterapred) |
| Standard of Care | Experimental | Drug: Assigned InterventionsArm1:) sirolimus and tacrolimus and prednisone group: Tacrolimus, The patient will receive 0.1-0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 5-12 ng/ml. Mycophenolate mofetil (NA )Stopped upon sirolimus initiation Sirolimus:1-5 mg/day PO if >40 kg / 1 mg/m²/day if <40 kg trough blood levels 5-12 ng/ml Prednisone:20 mg/day PO if >40 kg and 10 mg/day if <40 kg, adjust based on adverse effects. Arm 2) Standard Therapy Tacrolimus:0.1 to 0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 8-12 ng/ml Mycophenolate mofetil:750-1250 mg bid PO and adjust to tolerance (WBCs and GI side effects Sirolimus: NA Prednisone: Prednisone dose 20 mg/day PO if >40 kg and 10 mg/day if <40 kg, adjust based on adverse effect |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age: 18 or older.
- Recipient of a single or double pulmonary allograft at least twelve months before study entry.
- Clinically diagnosed BOS grade 1 or 2
- Receiving oral TAC-based immunosuppression according to institutional standards.
- Capable of understanding the purposes and risks of the study, has given written informed consent and agrees to comply with the study requirements and capable of protocol adherence.
Key exclusion criteria (15 listed)
- Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry.
- Mechanical ventilation.
- At screening FEV1 < 1 liter and/or < FEV1 of 25 % predicted.
- Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy.
- Women who breastfeed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Assigned InterventionsAlso: Tacrolimus, Mycophenolate mofetil, Prednisone, SirolimusThis is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs). Patients meeting entry criteria shall demonstrate a sustained decline in FEV1 having met stage 1 or 2 BOS. Patients randomized to the study arm, will be treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus and prednisone compared to those patients randomized to defined ST alone (tacrolimus, MMF and prednisone). The trial duration will be approximately 2 years for each subject randomized. Treatment compliance and safety will be monitored by clinic visits at 4-6 week intervals for the 2 year subject duration and will include standard physical examinations and monitoring of routine clinical and laboratory parameters including cause of hospitalizations and rate of adverse events including death in each group. T | Drug | Sirolimus and Tacrolimus and prednisone, Standard of Care |
Primary outcome
Death
Time frame: 2 years
Increase in motility
Re-Transplantation
Time frame: 2 years
Increase in re-transplantation from baseline
FEV1 (Forced Respiratory Volume in 1 second)
Time frame: 2 years
Greater or equal to 20% decline in FEV1 from randomization
2 secondary outcomes
FVC (Forced Vital Capacity)
Time frame: 2 years
FEF (forced expiratory flow)
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Results publication: PubMed 16407509Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50. doi: 10.1056/NEJMoa043204.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aldo T Iacono, MD principal investigator
University of Maryland, Baltimore
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Assigned Interventions in people with Disorder Related to Lung Transplantation and Chronic Rejection of Lung Transplant, run by University of Maryland, Baltimore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04415476, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.