Treatment of IPF With Laparoscopic Anti-Reflux Surgery

Study Overview
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Brief Summary
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This study will test the hypothesis that treatment with laparoscopic anti-reflux surgery in subjects with idiopathic pulmonary fibrosis (IPF) and abnormal gastroesophageal reflux (GER) will slow the decline of forced vital capacity (FVC) over 48 weeks.

Detailed Description
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This protocol proposes to test the following hypothesis: Treatment with laparoscopic anti-reflux surgery in subjects with idiopathic pulmonary fibrosis (IPF) and abnormal gastroesophageal (GER) reflux will slow the decline of forced vital capacity (FVC) over 48 weeks. This study will randomize approximately 58 subjects with IPF and abnormal acid reflux on 24-hour impedance / pH monitoring to laparoscopic anti-reflux surgery or standard care (randomization ratio 1:1). Subjects will be followed for 48 weeks or until the time of lung transplantation or death. We aim to achieve the following: determine the impact of laparoscopic anti-reflux surgery on change in FVC over 48 weeks in patients with IPF and abnormal GER; correlate the reduction in acid and non-acid reflux events with the change in FVC over 48 weeks in patients with IPF and abnormal GER; determine the safety of laparoscopic anti-reflux surgery in patients with IPF and abnormal GER; explore the impact of laparoscopic anti-reflux surgery on key secondary endpoints over 48 weeks in patients with IPF and abnormal GER; identify molecular markers of IPF disease activity and gastroesophageal reflux in biological samples from patients with IPF and abnormal GER.

Official Title
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Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients With Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis, Gastroesophageal Reflux

Intervention / Treatment
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* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of idiopathic pulmonary fibrosis Abnormal GER on 24-hour pH monitoring (DeMeester score > 14.7) Able to provide informed consent Willing to undergo laparoscopic anti-reflux surgery Exclusion Criteria: FVC < 50% predicted FEV1/FVC ratio < 0.65 Resting room air PaO2 < 60mm Hg Unable to walk 50 meters on 6 minute walk test Acute respiratory illness in last 12 weeks Experimental medication for IPF in last 28 days Listed for lung transplantation at screening Unable to safely undergo surgery History of esophageal / bariatric / gastric surgery History of cancer (other than non-melanoma skin cancer) in last 3 years Pregnant at time of screening or enrollment Unable to obtain pre-authorized approval from a third party payer for surgery and related costs Life expectancy < 48 weeks due to another illness BMI > 35 Known severe pulmonary hypertension (mean pressure > 35 mm Jg on RHC; RVSP > 50 mm Hg on ECHO)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Subjects to receive standard anti-reflux treatment per clinical discretion | |
| Active Comparator: Surgery<br>Subjects will receive laparoscopic fundoplication surgery | Procedure: Surgery<br>* Full fundoplication surgery for the treatment of abnormal GER<br>* Other names: Laparoscopic anti-reflux surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity (FVC) | Change in FVC (in liters) between enrollment and 48 weeks. | Baseline and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Change in acid and non-acid reflux events from baseline to week 48. All subjects answered questions related to their reflux using a Likert scale (0 = never, 1 =occasionally, 2 = sometimes, 3 = often, 4 = always). | Baseline and 48 weeks | 
| Safety of Laparoscopic Anti-reflux Surgery | Overall safety of laparoscopic anti-reflux surgery in patients with IPF and abnormal GER as measured by number of participants who experienced death, serious adverse event, or other (not including serious) adverse event. See Adverse Events section for additional details. | 48 weeks | 
| All-cause Mortality | Impact of anti-reflux surgery on all-cause mortality from enrollment to 48 weeks | 48 weeks | 
| Non-elective Hospitalization | Impact on non-elective hospitalizations from baseline to 48 weeks. | Baseline and 48 weeks | 
| Acute Exacerbations | Impact on acute exacerbations of IPF from baseline to week 48. | Baseline and 48 weeks | 
| University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOQB) Score | Change in UCSD SOQB score from baseline to week 48. The score range is 0-120. Higher scores indicate higher breathlessness. | Baseline and 48 weeks | 
| St. George's Respiratory Questionnaire (SGRQ) Score | Change in SGRQ score from baseline to week 48. The score range is 0-100. Higher scores indicate more limitations. | Baseline and 48 weeks | 
| 6-minute Walk Distance | Change in 6-minute walk distance from baseline to week 48 | Baseline and 48 weeks | 
| Cough Visual Analog Scale (VAS) | Change in VAS from baseline to week 48. The scale range is 1-100. Lower scores indicate no cough and 100 indicates the worst cough. | Baseline and 48 weeks | 
| High-Resolution CT (HRCT) Fibrosis Score. | Change in HRCT fibrosis score from baseline to week 48. HRCT Fibrosis score is calculated as a percentage. Higher percentage indicates more fibrosis. | Baseline to 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IPF, Idiopathic pulmonary fibrosis, Gastroesophageal reflux, GER, GERD