Disorder Related to Lung TransplantationPhase 2NCT03473340
Studying the Treatment Effect of Pirfenidone in Chronic Lung Allograft Dysfunction (STOP-CLAD)
A Phase 2 study testing Pirfenidone Capsule in people with Disorder Related to Lung Transplantation and Chronic Lung Allograft Dysfunction, run by University of Michigan at 1 site in United States.
Trial summary
Greater than 50% of lung transplant recipients show signs of chronic lung allograft dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and prolong allograft survival. 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 Lung Allograft Dysfunction
- What is being tested?
- Pirfenidone Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Apr 2018to 20 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Lung transplant recipients 18 years of age or older
- Greater than 6 months after single or bilateral lung transplantation
- Baseline FEV1 and FVC values (mean of two highest value measured 3 weeks apart) > 50% predicted (to assure viable graft)
- Diagnosis of CLAD (two consecutive spirometric values of FEV1 alone or both FEV1 and FVC < 80% of baseline)
Who cannot join
- Acute Rejection (AR) diagnosis by biopsy in the 28 days prior to enrollment
- Treatment with pulse steroids, Anti-thymocyte Globulin (ATG), extracorporeal photopheresis (ECP), plasmapheresis, or Immunoglobulin therapy aimed at CLAD within the 28 days prior to enrollment
- If the subject is receiving chronic Azithromycin therapy, the dose must be stable for the 28 days prior to enrollment
- Presence of active pulmonary infection at the time of enrollment as determined by an investigator in consultation with the treating pulmonologist
- Diagnosis of bronchial stenosis either a) requiring stenting, or b) thought to be responsible for the spirometric decline by principal investigator
- Abnormal liver function tests (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN), Alkaline phosphatase > 2.5 x ULN, total bilirubin > ULN) or known cirrhosis (>2 times upper limit of normal of AST/ALT/AP)
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- Total white blood cell (WBC) < 3.0 K/uL
- Moderate to Severe Renal insufficiency (CrCl <15 mL/min calculated by the Cockcroft-Gault equation)
- Use of any medication known to cause significant interactions with pirfenidone (strong CYP1A2 inhibitors such as Fluvoxamine or Enoxacin or inducers)
- Pregnancy or lactation. Women of child-bearing potential will have a pregnancy test at enrollment and must agree to maintain highly effective contraception with two methods of birth control from the date of consent through the end of the study.
- Tobacco use within 6 months
- History of alcohol abuse in the past 1 year as determined by the treating pulmonologist
- Any condition other than CLAD that will likely result in death in the next 1 year
- Any condition in the judgement of the principal investigator that would preclude participation in this study
- EKG with QTc interval > 500 msec at screening
- Listed for repeat lung transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Michigan
Ann Arbor, Michigan, 48109
About this study
Official title: A Phase Two Randomized, Double-blinded, Placebo-controlled Study Combining Physiological, Radiographic, and Biological Biomarkers to Study the Anti-fibrotic Effect of Pirfenidone in CLAD Post Lung-transplantation
Greater than 50% of lung transplant recipients show signs of chronic lung allograft dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and prolong allograft survival. This study investigates if Pirfenidone therapy will stabilize lung function decline and slow progression of Functional small airways disease (fSAD) in lung transplant recipients with CLAD.
Read the detailed description
The study aimed to enroll lung transplant recipients with an established diagnosis of CLAD. The patients were randomized to receive an anti-fibrotic drug Pirfenidone or Placebo pills for 6 month period. High-resolution CT scan of the chest was utilized to measure the primary endpoint of change in functional small airway disease (fSAD). Pulmonary function testing and spirometry were utilized to measure the secondary endpoint of change in FEV1 and FVC.
- Being tested
- Pirfenidone Capsule, Placebo Capsule
- Keywords
- CLAD, Chronic Rejection, Lung Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pirfenidone CapsuleDrug
Also called Esbriet
Dosing:
Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks
Placebo CapsuleDrug
Also called Placebo
Dosing:
- Days 1 through 7, 267 mg three times daily;
- Days 8 through 14, 534 mg three times daily;
- Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone Capsule | Experimental | Method of Administration: Oral (capsule)
Dosing:
* Days 1 through 7, 267 mg three times daily;
* Days 8 through 14, 534 mg three times daily;
* Days 15 through end of treatment (24 weeks), 801 mg three times daily Receives: Drug: Pirfenidone Capsule |
| Placebo Capsule | Placebo comparator | Method of Administration: Oral (capsule)
Dosing:
* Days 1 through 7, 267 mg three times daily;
* Days 8 through 14, 534 mg three times daily;
* Days 15 through end of treatment (24 weeks), 801 mg three times daily Receives: Drug: Placebo Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping
Evaluate if pirfenidone compared to placebo will stabilize progression of fSAD by comparison of inspiratory and expiratory high resolution computed tomography (HRCT) images through co-registration to provide quantitative measures of fSAD.
Measured: Baseline, 24 weeks
Secondary outcomes (4)
Change in Forced Expiratory Volume 1 Over 24 Weeks (FEV1)
Measured by spirometry
Measured: Baseline, 24 weeks
Change in Forced Vital Capacity (FVC) Over 24 Weeks
Measured by spirometry
Measured: Baseline, 24 weeks
Number of Adverse Events Related to Study Treatment
Safety of pirfenidone will be measured by adverse events determined to be related to the study drug through review of medical history, physical exam and laboratory findings.
Measured: 28 weeks
Number of Subjects With Treatment Intolerance
Subjects permanently discontinuing study medication before 24 weeks
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2018
- Study start27 Apr 2018
- Primary completion23 Jul 2021
- Study completion20 Aug 2021
Why it stopped: Slow and delayed recruitment due in part to COVID, led to a decision to end funding and terminate the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 MichiganThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Vibha Lama, University of Michigan
- Investigators
- Vibha Lama, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03473340
- Sponsor's protocol ID
- HUM00131610
- Status last verified
- Jul 2022
- First submitted
- 14 Mar 2018
- Last updated
- 17 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Combs MP, Belloli EA, Gargurevich N, Flaherty KR, Murray S, Galban CJ, Lama VN. Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study). J Heart Lung Transplant. 2024 Sep;43(9):1468-1477. doi: 10.1016/j.healun.2024.05.013. Epub 2024 May 23.
PubMed 38796045
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Two Randomized, Double-blinded, Placebo-controlled Study Combining Physiological, Radiographic, and Biological Biomarkers to Study the Anti-fibrotic Effect of Pirfenidone in CLAD Post Lung-transplantation
- ClinicalTrials.gov ID
- NCT03473340
- Acronym / sponsor ID
- HUM00131610
- Keywords
- CLAD, Chronic Rejection, Lung Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow and delayed recruitment due in part to COVID, led to a decision to end funding and terminate the trial.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 27 Apr 2018 (actual)
- Primary completion
- 23 Jul 2021 (actual)
- Study completion
- 20 Aug 2021 (actual)
- First posted
- 22 Mar 2018 (actual)
- Results
- Posted 17 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Greater than 50% of lung transplant recipients show signs of chronic lung allograft dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and prolong allograft survival. This study investigates if Pirfenidone therapy will stabilize lung function decline and slow progression of Functional small airways disease (fSAD) in lung transplant recipients with CLAD.
Detailed description
The study aimed to enroll lung transplant recipients with an established diagnosis of CLAD. The patients were randomized to receive an anti-fibrotic drug Pirfenidone or Placebo pills for 6 month period. High-resolution CT scan of the chest was utilized to measure the primary endpoint of change in functional small airway disease (fSAD). Pulmonary function testing and spirometry were utilized to measure the secondary endpoint of change in FEV1 and FVC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone Capsule | Experimental | Drug: Pirfenidone CapsuleMethod of Administration: Oral (capsule) Dosing: * Days 1 through 7, 267 mg three times daily; * Days 8 through 14, 534 mg three times daily; * Days 15 through end of treatment (24 weeks), 801 mg three times daily |
| Placebo Capsule | Placebo comparator | Drug: Placebo CapsuleMethod of Administration: Oral (capsule) Dosing: * Days 1 through 7, 267 mg three times daily; * Days 8 through 14, 534 mg three times daily; * Days 15 through end of treatment (24 weeks), 801 mg three times daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Lung transplant recipients 18 years of age or older
- Greater than 6 months after single or bilateral lung transplantation
- Baseline FEV1 and FVC values (mean of two highest value measured 3 weeks apart) > 50% predicted (to assure viable graft)
- Diagnosis of CLAD (two consecutive spirometric values of FEV1 alone or both FEV1 and FVC < 80% of baseline)
Key exclusion criteria (16 listed)
- Acute Rejection (AR) diagnosis by biopsy in the 28 days prior to enrollment
- Treatment with pulse steroids, Anti-thymocyte Globulin (ATG), extracorporeal photopheresis (ECP), plasmapheresis, or Immunoglobulin therapy aimed at CLAD within the 28 days prior to enrollment
- If the subject is receiving chronic Azithromycin therapy, the dose must be stable for the 28 days prior to enrollment
- Presence of active pulmonary infection at the time of enrollment as determined by an investigator in consultation with the treating pulmonologist
- Diagnosis of bronchial stenosis either a) requiring stenting, or b) thought to be responsible for the spirometric decline by principal investigator
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 |
|---|---|---|
| Pirfenidone CapsuleAlso: EsbrietDosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks | Drug | Pirfenidone Capsule |
| Placebo CapsuleAlso: PlaceboDosing: * Days 1 through 7, 267 mg three times daily; * Days 8 through 14, 534 mg three times daily; * Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks | Drug | Placebo Capsule |
Primary outcome
Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping
Time frame: Baseline, 24 weeks
Evaluate if pirfenidone compared to placebo will stabilize progression of fSAD by comparison of inspiratory and expiratory high resolution computed tomography (HRCT) images through co-registration to provide quantitative measures of fSAD.
4 secondary outcomes
Change in Forced Expiratory Volume 1 Over 24 Weeks (FEV1)
Time frame: Baseline, 24 weeks
Change in Forced Vital Capacity (FVC) Over 24 Weeks
Time frame: Baseline, 24 weeks
Number of Adverse Events Related to Study Treatment
Time frame: 28 weeks
Number of Subjects With Treatment Intolerance
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38796045Combs MP, Belloli EA, Gargurevich N, Flaherty KR, Murray S, Galban CJ, Lama VN. Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study). J Heart Lung Transplant. 2024 Sep;43(9):1468-1477. doi: 10.1016/j.healun.2024.05.013. Epub 2024 May 23.
- 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.
Vibha Lama, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pirfenidone Capsule in people with Disorder Related to Lung Transplantation and Chronic Lung Allograft Dysfunction, run by University of Michigan at 1 site in United States.
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 4 inclusion and 16 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: stopped early, as of the sponsor's last update on 17 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 17 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping (time frame: Baseline, 24 weeks). 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 NCT03473340, 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 17 Aug 2022.