Gastroesophageal Reflux, Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Idiopathic pulmonary fibrosis, IPF, Gastroesophageal reflux, GER, GERD
Brief summary
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
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.
Interventions
PROCEDURESurgery
Full fundoplication surgery for the treatment of abnormal GER
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity (FVC) | Baseline and 48 weeks | Change in FVC (in liters) between enrollment and 48 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Laparoscopic Anti-reflux Surgery | 48 weeks | 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. |
| All-cause Mortality | 48 weeks | Impact of anti-reflux surgery on all-cause mortality from enrollment to 48 weeks |
| Non-elective Hospitalization | Baseline and 48 weeks | Impact on non-elective hospitalizations from baseline to 48 weeks. |
| Acute Exacerbations | Baseline and 48 weeks | Impact on acute exacerbations of IPF from baseline to week 48. |
| Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Baseline and 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). |
| St. George's Respiratory Questionnaire (SGRQ) Score | Baseline and 48 weeks | Change in SGRQ score from baseline to week 48. The score range is 0-100. Higher scores indicate more limitations. |
| 6-minute Walk Distance | Baseline and 48 weeks | Change in 6-minute walk distance from baseline to week 48 |
| Cough Visual Analog Scale (VAS) | Baseline and 48 weeks | 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. |
| High-Resolution CT (HRCT) Fibrosis Score. | Baseline to 48 weeks | Change in HRCT fibrosis score from baseline to week 48. HRCT Fibrosis score is calculated as a percentage. Higher percentage indicates more fibrosis. |
| University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOQB) Score | Baseline and 48 weeks | Change in UCSD SOQB score from baseline to week 48. The score range is 0-120. Higher scores indicate higher breathlessness. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Subjects to receive standard anti-reflux treatment per clinical discretion | 29 |
| Surgery Subjects will receive laparoscopic fundoplication surgery
Surgery: Full fundoplication surgery for the treatment of abnormal GER | 29 |
| Total | 58 |
Baseline characteristics
| Characteristic | Control | Total | Surgery |
|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 7.35 | 69.9 years STANDARD_DEVIATION 6.67 | 70.6 years STANDARD_DEVIATION 5.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 55 Participants | 27 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 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 | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 27 Participants | 54 Participants | 27 Participants |
| Region of Enrollment United States | 29 participants | 58 participants | 29 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 1 Participants |
| Sex: Female, Male Male | 19 Participants | 47 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 29 | 1 / 29 |
| other Total, other adverse events | 0 / 29 | 9 / 29 |
| serious Total, serious adverse events | 8 / 29 | 5 / 29 |
Outcome results
Primary
Forced Vital Capacity (FVC)
Change in FVC (in liters) between enrollment and 48 weeks.
Time frame: Baseline and 48 weeks
Population: Randomized patients
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Forced Vital Capacity (FVC) | -0.13 liters |
| Surgery | Forced Vital Capacity (FVC) | -0.05 liters |
Secondary
6-minute Walk Distance
Change in 6-minute walk distance from baseline to week 48
Time frame: Baseline and 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | 6-minute Walk Distance | 9.13 meters |
| Surgery | 6-minute Walk Distance | 16.54 meters |
Secondary
Acute Exacerbations
Impact on acute exacerbations of IPF from baseline to week 48.
Time frame: Baseline and 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Acute Exacerbations | 4 Participants |
| Surgery | Acute Exacerbations | 1 Participants |
Secondary
All-cause Mortality
Impact of anti-reflux surgery on all-cause mortality from enrollment to 48 weeks
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | All-cause Mortality | 4 Participants |
| Surgery | All-cause Mortality | 1 Participants |
Secondary
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).
Time frame: Baseline and 48 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Do you get heartburn? | -0.65 score on a scale | Standard Deviation 1.09 |
| Control | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Does your stomach get bloated? | -0.40 score on a scale | Standard Deviation 0.82 |
| Control | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Do you get bitter liquid (acid) in throat? | -0.63 score on a scale | Standard Deviation 1.01 |
| Control | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Do you burp a lot? | -0.25 score on a scale | Standard Deviation 0.72 |
| Surgery | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Do you burp a lot? | -0.74 score on a scale | Standard Deviation 1.18 |
| Surgery | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Do you get heartburn? | -1.04 score on a scale | Standard Deviation 0.95 |
| Surgery | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Do you get bitter liquid (acid) in throat? | -1.13 score on a scale | Standard Deviation 0.9 |
| Surgery | Change in Score From Baseline for Acid and Non-acid Reflux Events at 48 Weeks | Does your stomach get bloated? | -0.39 score on a scale | Standard Deviation 0.99 |
Secondary
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.
Time frame: Baseline and 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Cough Visual Analog Scale (VAS) | 7.15 score on a scale |
| Surgery | Cough Visual Analog Scale (VAS) | 4.74 score on a scale |
Secondary
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.
Time frame: Baseline to 48 weeks
Population: Data are not available to be reported due to inability to obtain imaging data on participants and generate a score.
Secondary
Non-elective Hospitalization
Impact on non-elective hospitalizations from baseline to 48 weeks.
Time frame: Baseline and 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Non-elective Hospitalization | 8 Participants |
| Surgery | Non-elective Hospitalization | 5 Participants |
Secondary
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.
Time frame: 48 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Safety of Laparoscopic Anti-reflux Surgery | All Cause Mortality | 4 Participants |
| Control | Safety of Laparoscopic Anti-reflux Surgery | Serious Adverse Events | 8 Participants |
| Control | Safety of Laparoscopic Anti-reflux Surgery | Other (Not Including Serious) Adverse Events | 0 Participants |
| Surgery | Safety of Laparoscopic Anti-reflux Surgery | All Cause Mortality | 1 Participants |
| Surgery | Safety of Laparoscopic Anti-reflux Surgery | Serious Adverse Events | 5 Participants |
| Surgery | Safety of Laparoscopic Anti-reflux Surgery | Other (Not Including Serious) Adverse Events | 9 Participants |
Secondary
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.
Time frame: Baseline and 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | St. George's Respiratory Questionnaire (SGRQ) Score | -3.18 score on a scale |
| Surgery | St. George's Respiratory Questionnaire (SGRQ) Score | 1.04 score on a scale |
Secondary
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.
Time frame: Baseline and 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOQB) Score | 0.69 score on a scale |
| Surgery | University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOQB) Score | 0.71 score on a scale |