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Nintedanib in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome Grade 0p-1-2 (INFINITx-BOS)

Primary Purpose

Lung-transplant Recipients

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Nintedanib
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung-transplant Recipients focused on measuring Nintedanib, lung transplantation, bronchiolitis obliterans syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent signed prior to entry into the trial
  2. Patients ≥18 years of age when signing his/her informed consent
  3. Patients at least at 6 months post-LTx
  4. Single- or double-LTx or combined cardio-pulmonary LTx are eligible
  5. Patients must have diagnosis of BOS defined as a decrement of 10% or more in forced expiratory volume in 1 seconde (FEV1) compared to post-transplant baseline FEV1 individualized for each patient according to ISHLT definition. The documented post-LTx baseline value of FEV1 is defined as the mean of the 2 highest values measured at least 3 weeks apart according to ISHLT criteria, and post-LTx VC measurements
  6. Patients must have BOS grade 0p, 1 or 2
  7. Patients must have documented progressive BOS as demonstrated by the following criteria: at least 3 FEV1 and VC measurements in the last 12 months prior V1, each at least 3 weeks apart, with a total decline of at least 200ml in FEV1 in these last 12 months AND FEV1/VC<0.7
  8. Azithromycin therapy for at least 4 weeks prior to V1, with an Azithromycin dose of minimum 250 mg/day at least 3 times per week as this is considered standard therapy for bronchiolitis obliterans syndrome

Exclusion Criteria:

Related to LTx

  1. Criteria of restrictive allograft syndrome (RAS) at V0, including the following: (1) Decline of VC < 20% of best post-LTx value (FVCBest is defined as the average of the two FVCs associated with the two PFTs used in FEV1 baseline calculation for CLAD diagnosis) AND FEV1/VC > 0.7 AND (2) Thorax HRCT at entry demonstrate new significant findings which are compatible with RAS like interstitial fibrosis, consolidation, appearances suggesting Restrictive Allograft Syndrome (RAS)
  2. FEV1 and/or FV and/or TLC decline related to other nonCLAD causes (eg Diaphragm dysfunction, pneumothorax or pleural effusion, evolutive bronchial stricture within the previous 3 months)
  3. At V0, patients who already have developed severe BOS grade 3
  4. Patients with severe comorbidity complicating CLAD which might determine the prognosis and functional level of the patient (e.g. evolutive invasive aspergillosis or mycobacterial infection within the last 3 months, active malignant disease within the last 12 months)
  5. At visit V1 (end of screening period), diagnosis of documented acute cellular (AR) perivascular rejection higher than grade A1 within the 4 prior weeks OR diagnosis of acute antibody-mediated rejection within the 4 prior weeks, based on presence of all 4 following criteria: 1) acute lung allograft dysfunction, 2) detection of donor-specific antibodies, 3) histological findings compatible with AMR on transbronchial lung biopsy TBBx, and 4) detection of C4d > 50% on TBBx
  6. At visit V1 (end of screening period), diagnosis of documented acute pulmonary infection within the 2 prior weeks, on the basis of the following: 1) clinical, radiological and physiological deterioration; AND 2) isolation of an organism from a clinically relevant BAL fluid culture; AND 3) antibiotic therapy resulting in a full recovery and return to pre-morbid lung function
  7. Previous treatment with Nintedanib after the date of lung transplantation (Treatment with Nintedanib before lung transplantation is not an exclusion criteria)
  8. Ongoing treatment with photopheresis at V1 or planned treatment with photopheresis within the study period.

    Laboratory parameter thresholds

  9. Within the 2 weeks prior to V1, renal insufficiency with following criteria: Creatinine clearance <30 ml/min estimated by the Cockcroft-Gault equation
  10. Within the 2 weeks prior to V1, any of the following liver test criteria above the specified limit: Total bilirubin > 1.5 above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert's syndrome). Aspartate or alanine aminotransferase (AST or ALT) >3 × ULN (refer to the protocole, for the management of liver enzyme elevation).

    General exclusion criteria

  11. Pregnancy or lactation (women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent to three months after the end of the patient study participation)
  12. Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit (V0)
  13. Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment
  14. Patients not able to understand and follow study procedures including completion of self-administered questionnaires without help.

    Other diseases

  15. Cardiac disease: (1) History of myocardial infarction within 6 months of visit 1 or unstable angina within 6 months of visit 1; (2) Presence of aortic stenosis (AS) per investigator judgement at visit 1; (3) Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25% per investigator judgement at visit 1
  16. Known allergy or hypersensitivity to Nintedanib or intolerance to nintedanib, peanut or soya, or any other components of the study medication
  17. Bleeding Risk: Known genetic predisposition to bleeding; Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin, etc.) or high dose antiplatelet therapy (acetyl salicylic acid >325 mg/day, or clopidogrel >75 mg/day) [NB: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s.c. per day), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited]; History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1; History of haemoptysis or haematuria within 3 months prior to visit 1, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1; International normalised ratio (INR) > 2 at visit 1; Prothrombin time (PT) and activated partial thromboplastin time (aPTT) > 150% of institutional ULN at visit 1
  18. Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment)
  19. Planned major surgery during the trial participation
  20. History of thrombotic event (including stroke and transient ischemic attack) within 6 months of visit 1
  21. Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG) per investigator judgement at visit 1
  22. i) Hypotension (systolic blood pressure [SBP] < 90 mm Hg or diastolic blood pressure [DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1 ii) Uncontrolled systemic hypertension (SBP > 160 mmHg; DBP > 100 mmHg) at visit 1
  23. Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose to priapism
  24. Retinitis pigmentosa, or History of vision loss, or History of nonarteritic ischemic optic neuropathy
  25. Ongoing treatment with pirfenidone at V1 or planned treatment with pirfenidone within the study period.

Sites / Locations

  • Foch HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nintedanib

Placebo

Arm Description

Eligible LTx recipients with BOS receive Nintedanib treatment at a dose of 150 mg twice daily (bid) for 6 months

Eligible LTx recipients with BOS receive Nintedanib 150 mg BID matching placebo treatment for 6 months

Outcomes

Primary Outcome Measures

Nintedanib efficacy in the reduction of the rate of decline of FEV1 (forced expiratory volume in 1 sec) in BOS post-LTx grade 0p-1-2 at a dose of 150 mg twice daily (bid) compared to placebo over 6 months
The absolute difference of FEV1 in mL over 6 months of treatment defined by the rate of decline between inclusion (Visit 1) and month 6 (Visit 4) will be compared between Nintedanib versus Placebo groups

Secondary Outcome Measures

Nintedanib efficacy on exercise tolerance in LTx recipients
Nintedanib efficacy on exercise tolerance will be assessed by the absolute change from baseline in the 6-min Walking Test at month 6 in Nintedanib group compared to Placebo group
Nintedanib efficacy on quality of life improvement in LTx recipients
Nintedanib efficacy on quality of life improvement will be assessed by the absolute change from baseline in SGRQ (Saint George's Respiratory Questionnaire) total score at month 6 in Nintedanib group compared to Placebo group
Nintedanib efficacy to hamper FEV1 decrease in LTx recipients
Nintedanib efficacy to hamper FEV1 decrease will be assessed by the absolute change of FEV1 in mL at month 6 by a repeated FEV1 measurements (at month 0, month 1, month 3, month 6) in Nintedanib group compared to Placebo group
Nintedanib efficacy to hamper progression of BOS in LTx recipients
Nintedanib efficacity to hamper progression of BOS will be assessed by the proportion of patients with change in BOS grade and graft failure (defined as death or retransplantation) in Nintedanib group compared to Placebo group
Nintedanib efficacy on the change of Oxygen saturation in LTx recipients
Nintedanib efficacity on the change of Oxygen saturation will be assessed by the absolute change from baseline in Oxygen saturation (expressed in percent) rest evaluated from baseline at month 6 in Nintedanib group compared to Placebo group
Nintedanib tolerance in LTx recipients
Nintedanib tolerance in lung-transplant recipients over 6 months will be assessed in comparing occurrence of adverse events between both arms (Nintedanib vs Placebo)
Explanatory parameters of fibrotic pathways
Explanatory parameters of fibrotic pathways will be assessed by absolute changes of biomarkers of alveolar cells injury (Krebs von den Lungen-6 (KL6), surfactant apoprotein D (SPD), and growth factors as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)) since baseline at month 6

Full Information

First Posted
September 6, 2017
Last Updated
October 3, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT03283007
Brief Title
Nintedanib in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome Grade 0p-1-2
Acronym
INFINITx-BOS
Official Title
A Multi-center, Randomised, Double-blind Trial of Nintedanib in Lung Transplant (LTx) Recipients With Bronchiolitis Obliterans Syndrome (BOS) Grade 0p-1-2
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 30, 2019 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Lung transplantation (TxP) is now a validated treatment of end-stage pulmonary diseases, but long-term graft and patient survival are still hampered by the development of chronic allograft dysfunction (CLAD) affecting > 50% of patients. The investigators propose to conduct a phase III clinical randomized trial that will assess the efficacy of Nintedanib to hamper the lung decline in LTx recipients with BOS. This is the first trial testing this molecule in lung Tx recipients. If case of demonstrated effectiveness of Nintedanib, the benefit for lung transplant patients carrying a BO is high in terms of stabilization of lung function and enhancement of survival.
Detailed Description
Introduction: Lung transplantation (TxP) is now a validated treatment of end-stage pulmonary diseases, but long-term graft and patient survival are still hampered by the development of chronic allograft dysfunction (CLAD) affecting > 50% of patients. Obliterative bronchiolitis (OB), the obstructive CLAD, is the most common manifestation of CLAD, and affects > 50% of recipients who survive the early post-transplant period. OB is thought to arise from repeated injury to graft epithelial cells, leading to fibrous scarring and obliteration of the small airway lumen, as a result of dysregulated fibrotic repair and loss of peribronchial microvasculature. The patchy histopathologic distribution at onset makes it difficult to confirm histopathologically the diagnosis of OB from lung specimens. Hence, bronchiolitis obliterans syndrome (BOS) has become a generally accepted surrogate diagnostic of OB, characterized physiologically by progressive airflow limitation, with a median monthly decline of FEV1 of about 50 ml. Survival after onset of BOS is poor, reported as < 50% at 3 years after onset of disease, due to end-stage respiratory failure. Thus far, there is currently no approved treatment to stabilize BOS disease, and especially no treatment addressing the fibrotic lung graft manifestation of BOS. The crucial role of a dysregulated fibrotic repair has now been demonstrated in BOS, with the following: (i) Architectural remodelling with fibrosis and scarring of airways involving myofibroblasts; (ii) Increased extracellular matrix synthetic; (iii) Epithelial-mesenchymal transition mechanism; (iv) Role of growth factors PDGF, VEGF, FGF, and IGF-1 shown in BO mechanisms (animals and humans studies). These data strongly suggest the potential role of tyrosine kinase inhibitors (TKI) that target these growth factors involved in the post-TxP BO. In this axis, the new TKI Nintedanib, which has recently been demonstrated as effective in the treatment of idiopathic pulmonary fibrosis (IPF) in large-scale randomized studies (8) appears as a candidate molecule capable of stopping the fibroproliferative process and stabilize the development of a CLAD after TxP. Whereas Nintedanib is a validated and available treatment in patients with IPF, paucity of data are currently available in lung-transplant recipients. Primary objective: to assess Nintedanib efficacy in the reduction of the rate of decline of FEV1 (forced expiratory volume in 1 sec) in BOS post-LTx at a dose of 150 mg twice daily (bid) compared to placebo over 6 months. Secondary objectives: to assess Nintedanib efficacy and tolerance in the treatment of BOS grade 0p-1-2 post-lung transplantation. Experimental design: a 2 groups parallel, randomized, prospective multicentric placebo-controlled phase III trial to assess Nintedanib superiority versus placebo. Eligible LTx recipients with BOS are to be randomized in a 1:1 ratio to receive either Nintedanib 150 mg BID or the matching placebo treatment for 6 months. The follow-up of patients with BOS included in the trial will be similar to usual and standard care in both arms of the study (Nintedanib group and placebo group). The intervention group is expected to be beneficial compared to the placebo group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung-transplant Recipients
Keywords
Nintedanib, lung transplantation, bronchiolitis obliterans syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nintedanib
Arm Type
Experimental
Arm Description
Eligible LTx recipients with BOS receive Nintedanib treatment at a dose of 150 mg twice daily (bid) for 6 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible LTx recipients with BOS receive Nintedanib 150 mg BID matching placebo treatment for 6 months
Intervention Type
Drug
Intervention Name(s)
Nintedanib
Intervention Description
Eligible LTx recipients with BOS receive Nintedanib treatment at a dose of 150 mg twice daily (bid) for 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Eligible LTx recipients with BOS receive Nintedanib 150 mg BID matching placebo treatment for 6 months
Primary Outcome Measure Information:
Title
Nintedanib efficacy in the reduction of the rate of decline of FEV1 (forced expiratory volume in 1 sec) in BOS post-LTx grade 0p-1-2 at a dose of 150 mg twice daily (bid) compared to placebo over 6 months
Description
The absolute difference of FEV1 in mL over 6 months of treatment defined by the rate of decline between inclusion (Visit 1) and month 6 (Visit 4) will be compared between Nintedanib versus Placebo groups
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Nintedanib efficacy on exercise tolerance in LTx recipients
Description
Nintedanib efficacy on exercise tolerance will be assessed by the absolute change from baseline in the 6-min Walking Test at month 6 in Nintedanib group compared to Placebo group
Time Frame
6 months
Title
Nintedanib efficacy on quality of life improvement in LTx recipients
Description
Nintedanib efficacy on quality of life improvement will be assessed by the absolute change from baseline in SGRQ (Saint George's Respiratory Questionnaire) total score at month 6 in Nintedanib group compared to Placebo group
Time Frame
6 months
Title
Nintedanib efficacy to hamper FEV1 decrease in LTx recipients
Description
Nintedanib efficacy to hamper FEV1 decrease will be assessed by the absolute change of FEV1 in mL at month 6 by a repeated FEV1 measurements (at month 0, month 1, month 3, month 6) in Nintedanib group compared to Placebo group
Time Frame
6 months
Title
Nintedanib efficacy to hamper progression of BOS in LTx recipients
Description
Nintedanib efficacity to hamper progression of BOS will be assessed by the proportion of patients with change in BOS grade and graft failure (defined as death or retransplantation) in Nintedanib group compared to Placebo group
Time Frame
6 months
Title
Nintedanib efficacy on the change of Oxygen saturation in LTx recipients
Description
Nintedanib efficacity on the change of Oxygen saturation will be assessed by the absolute change from baseline in Oxygen saturation (expressed in percent) rest evaluated from baseline at month 6 in Nintedanib group compared to Placebo group
Time Frame
6 months
Title
Nintedanib tolerance in LTx recipients
Description
Nintedanib tolerance in lung-transplant recipients over 6 months will be assessed in comparing occurrence of adverse events between both arms (Nintedanib vs Placebo)
Time Frame
6 months
Title
Explanatory parameters of fibrotic pathways
Description
Explanatory parameters of fibrotic pathways will be assessed by absolute changes of biomarkers of alveolar cells injury (Krebs von den Lungen-6 (KL6), surfactant apoprotein D (SPD), and growth factors as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)) since baseline at month 6
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent signed prior to entry into the trial Patients ≥18 years of age when signing his/her informed consent Patients at least at 6 months post-LTx Single- or double-LTx or combined cardio-pulmonary LTx are eligible Patients must have diagnosis of BOS defined as a decrement of 10% or more in forced expiratory volume in 1 seconde (FEV1) compared to post-transplant baseline FEV1 individualized for each patient according to ISHLT definition. The documented post-LTx baseline value of FEV1 is defined as the mean of the 2 highest values measured at least 3 weeks apart according to ISHLT criteria, and post-LTx VC measurements Patients must have BOS grade 0p, 1 or 2 Patients must have documented progressive BOS as demonstrated by the following criteria: at least 3 FEV1 and VC measurements in the last 12 months prior V1, each at least 3 weeks apart, with a total decline of at least 200ml in FEV1 in these last 12 months AND FEV1/VC<0.7 Azithromycin therapy for at least 4 weeks prior to V1, with an Azithromycin dose of minimum 250 mg/day at least 3 times per week as this is considered standard therapy for bronchiolitis obliterans syndrome Exclusion Criteria: Related to LTx Criteria of restrictive allograft syndrome (RAS) at V0, including the following: (1) Decline of VC < 20% of best post-LTx value (FVCBest is defined as the average of the two FVCs associated with the two PFTs used in FEV1 baseline calculation for CLAD diagnosis) AND FEV1/VC > 0.7 AND (2) Thorax HRCT at entry demonstrate new significant findings which are compatible with RAS like interstitial fibrosis, consolidation, appearances suggesting Restrictive Allograft Syndrome (RAS) FEV1 and/or FV and/or TLC decline related to other nonCLAD causes (eg Diaphragm dysfunction, pneumothorax or pleural effusion, evolutive bronchial stricture within the previous 3 months) At V0, patients who already have developed severe BOS grade 3 Patients with severe comorbidity complicating CLAD which might determine the prognosis and functional level of the patient (e.g. evolutive invasive aspergillosis or mycobacterial infection within the last 3 months, active malignant disease within the last 12 months) At visit V1 (end of screening period), diagnosis of documented acute cellular (AR) perivascular rejection higher than grade A1 within the 4 prior weeks OR diagnosis of acute antibody-mediated rejection within the 4 prior weeks, based on presence of all 4 following criteria: 1) acute lung allograft dysfunction, 2) detection of donor-specific antibodies, 3) histological findings compatible with AMR on transbronchial lung biopsy TBBx, and 4) detection of C4d > 50% on TBBx At visit V1 (end of screening period), diagnosis of documented acute pulmonary infection within the 2 prior weeks, on the basis of the following: 1) clinical, radiological and physiological deterioration; AND 2) isolation of an organism from a clinically relevant BAL fluid culture; AND 3) antibiotic therapy resulting in a full recovery and return to pre-morbid lung function Previous treatment with Nintedanib after the date of lung transplantation (Treatment with Nintedanib before lung transplantation is not an exclusion criteria) Ongoing treatment with photopheresis at V1 or planned treatment with photopheresis within the study period. Laboratory parameter thresholds Within the 2 weeks prior to V1, renal insufficiency with following criteria: Creatinine clearance <30 ml/min estimated by the Cockcroft-Gault equation Within the 2 weeks prior to V1, any of the following liver test criteria above the specified limit: Total bilirubin > 1.5 above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert's syndrome). Aspartate or alanine aminotransferase (AST or ALT) >3 × ULN (refer to the protocole, for the management of liver enzyme elevation). General exclusion criteria Pregnancy or lactation (women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent to three months after the end of the patient study participation) Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit (V0) Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment Patients not able to understand and follow study procedures including completion of self-administered questionnaires without help. Other diseases Cardiac disease: (1) History of myocardial infarction within 6 months of visit 1 or unstable angina within 6 months of visit 1; (2) Presence of aortic stenosis (AS) per investigator judgement at visit 1; (3) Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25% per investigator judgement at visit 1 Known allergy or hypersensitivity to Nintedanib or intolerance to nintedanib, peanut or soya, or any other components of the study medication Bleeding Risk: Known genetic predisposition to bleeding; Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin, etc.) or high dose antiplatelet therapy (acetyl salicylic acid >325 mg/day, or clopidogrel >75 mg/day) [NB: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s.c. per day), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited]; History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1; History of haemoptysis or haematuria within 3 months prior to visit 1, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1; International normalised ratio (INR) > 2 at visit 1; Prothrombin time (PT) and activated partial thromboplastin time (aPTT) > 150% of institutional ULN at visit 1 Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment) Planned major surgery during the trial participation History of thrombotic event (including stroke and transient ischemic attack) within 6 months of visit 1 Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG) per investigator judgement at visit 1 i) Hypotension (systolic blood pressure [SBP] < 90 mm Hg or diastolic blood pressure [DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1 ii) Uncontrolled systemic hypertension (SBP > 160 mmHg; DBP > 100 mmHg) at visit 1 Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose to priapism Retinitis pigmentosa, or History of vision loss, or History of nonarteritic ischemic optic neuropathy Ongoing treatment with pirfenidone at V1 or planned treatment with pirfenidone within the study period.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier Brugière, MD, PhD
Phone
(0)1 46 25 36 01
Ext
+33
Email
o.brugiere@hopital-foch.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Brugière, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Foch Hospital
City
Suresnes
ZIP/Postal Code
92150
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier Brugière, MD, PhD
Phone
(0)1 46 25 36 01
Ext
+33
Email
o.brugiere@hopital-foch.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Nintedanib in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome Grade 0p-1-2

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