GERDPhase 3NCT01265550
A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors
A Phase 3 study testing Nissen fundoplication, baclofen and Desipramine in people with GERD, run by VA Office of Research and Development at 15 sites in United States.
Trial summary
Background: Gastroesophageal reflux disease (GERD), which affects at least 20% of adult Americans, may be especially common and severe in Veteran patients. Proton pump inhibitors (PPIs), which block gastric acid production, are the most effective medications for GERD, and the VA spends more than $177 million each year… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- GERD
- What is being tested?
- Nissen fundoplication, baclofen and Desipramine
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 366 participants
- Where
- 15 sitesUnited States
- Study dates
- 13 Aug 2012to 30 Dec 2016
- Phase
- Phase 3
- 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 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-70 years
- History of heartburn (defined as a burning sensation in the retrosternal area of the chest) that is refractory to antisecretory medications
- Initial GERD-HRQL:
- Total score must be at least 6 and at least one of the six heartburn questions must be scored at least 2
- GERD-HRQL after two weeks of treatment with omeprazole:
- Total score must be >50% of the initial GERD-HRQL score and at least one of the six heartburn questions must be scored at least 2
Show all 9Show fewer
- Either or both of the following by baseline esophageal pH/multichannel intraluminal impedance (MII) monitoring in patients on omeprazole 20 mg two times a day (BID):
- Positive symptom association probability (SAP) (>95%) for acid reflux, non-acid reflux or all reflux.
- Abnormal acid reflux (esophageal pH<4 for at least 4.2% of the 24-hour monitoring period)
Who cannot join
- Patients who do not have heartburn, defined as a burning sensation in the chest
- Patients unwilling or unable to provide informed consent
- Pregnancy or women unwilling to use effective contraception
- Age <18 or >70 years
- History of surgery on the stomach or esophagus
- History of seizure disorder
Show all 40Show fewer
- History of heart block
- Allergy to or previous inability to tolerate study medications (omeprazole, baclofen, desipramine)
- Esophageal varices
- Cirrhosis
- Co-morbidity of sufficient severity to preclude elective surgery (e.g. pulmonary, cardiac, renal, liver disease)
- History of disorders that can cause medically-refractory "GERD symptoms" (eosinophilic esophagitis, neoplasms of the upper gastrointestinal tract, gastroparesis, achalasia)
- Myocardial infarction within the past 6 months
- History of schizophrenia
- Current use of clopidogrel
- Patients who have a contraindication to omeprazole or baclofen or who require therapy with a medication that has a clinically important drug interaction with omeprazole or baclofen.
- Patients who, in the judgment of the PI, are not suitable candidates for therapy with a study medication (omeprazole, baclofen, desipramine)
- Initial GERD-HRQL score: Total score <6 and/or all heartburn scores <2
- Inability to tolerate omeprazole during the 2-week treatment phase (before randomization)
- GERD-HRQL after two weeks of treatment with omeprazole: Total score less than or equal to 50% of initial GERD-HRQL score and/or all heartburn scores <2
- Laboratory abnormalities including:
- Platelet count <100,000
- international normalized ratio (INR) >1.5 (off anticoagulants)
- Serum creatinine >2.0 mg per deciliter
- Endoscopic abnormalities including:
- Los Angeles Classification of Oesophagitis (LA grade) C or D reflux esophagitis
- Active ulceration of the esophagus that is not due to reflux esophagitis
- Candida esophagitis
- Esophageal varices
- Active ulceration of the stomach and/or duodenum
- Neoplasm of the esophagus, stomach or duodenum
- Gastric outlet obstruction
- Eosinophilic esophagitis at least (15 eosinophils per high power field in any esophageal biopsy specimen)
- Manometric abnormalities including:
- Achalasia
- Complete aperistalsis
- Negative SAP ( 95%) for acid reflux, non-acid reflux and all reflux on baseline combined esophageal pH/MII monitoring and normal acid reflux (esophageal pH<4 for <4.2% of the 24-hour monitoring period)
- Study surgeon identifies a contraindication to laparoscopic Nissen fundoplication
- Morbid obesity (BMI at least 40)
- Large paraesophageal hernia
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
Baltimore, Maryland, 21201
Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, 35233
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030
Kansas City VA Medical Center, Kansas City, MO
Kansas City, Missouri, 64128
VA Loma Linda Healthcare System, Loma Linda, CA
Loma Linda, California, 92357
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, 90822
Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC
Salisbury, North Carolina, 28144
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108
Syracuse VA Medical Center, Syracuse, NY
Syracuse, New York, 13210
Southern Arizona VA Health Care System, Tucson, AZ
Tucson, Arizona, 85723
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
West Haven, Connecticut, 06516
About this study
Official title: CSP #573 - A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors
Background: Gastroesophageal reflux disease (GERD), which affects at least 20% of adult Americans, may be especially common and severe in Veteran patients. Proton pump inhibitors (PPIs), which block gastric acid production, are the most effective medications for GERD, and the VA spends more than $177 million each year on outpatient PPI prescriptions. PPIs do not prevent the reflux of non-acidic material and do not completely eliminate esophageal acid exposure, however, and bothersome GERD symptoms persist in approximately 40% of patients treated with PPIs. Recent studies using the new technique of esophageal pH/ impedance monitoring, which detects the reflux of both acidic and non-acidic materials, have shown that PPI-resistant GERD symptoms correlate with episodes of reflux (acidic and/or non-acidic) in approximately one-half of patients. For those patients, an antireflux operation might relieve symptoms and obviate the expense of ineffective PPI therapy, but the efficacy of modern, laparoscopic fundoplication in this regard is not clear. For patients with PPI-resistant GERD symptoms, furthermore, the efficacy of medications that that can prevent gastroesophageal reflux (e.g. baclofen) or diminish pain of esophageal origin (e.g. neurotropic agents like desipramine) also is not clear. Study Hypothesis: Laparoscopic antireflux surgery (Nissen fundoplication) is superior to medical therapy (PPIs plus baclofen and desipramine) for GERD patients who, while on PPIs, have persistent episodes of heartburn that are associated with reflux episodes or with abnormal esophageal acid exposure by esophageal pH/impedance monitoring.
Study Goals: The primary goal is to compare the efficacy of laparoscopic Nissen fundoplication and medical therapy (PPIs plus baclofen and desipramine) for GERD patients who, while on PPIs, have persistent episodes of heartburn that are associated with reflux episodes or with abnormal esophageal acid exposure by esophageal pH/impedance monitoring, and to compare the efficacy of each therapy with placebo. Secondary goals are: 1) To determine the frequency with which non-GERD disorders underlie "PPI failure," 2) To determine the frequency of functional gastrointestinal symptoms, anxiety and depression in patients who have persistent heartburn while on PPIs, 3) To determine whether functional gastrointestinal symptoms, anxiety and depression is associated with the outcomes of medical and surgical therapies, and 4) To determine whether the outcome of Nissen fundoplication is associated with adherence to technical aspects of the operation.
Study Design: Up to 16 VA medical centers, there will be a 30-month recruitment period to enroll 108 patients with heartburn that is refractory to PPI therapy. Patients will have their baseline GERD symptoms scored using the GERD Health-Related Quality of Life (GERD-HRQL) index, and will have endoscopy, esophageal manometry and esophageal pH/impedance monitoring while on PPI therapy. Patients who have episodes of heartburn that are associated with reflux episodes or with abnormal esophageal acid exposure by esophageal pH/impedance monitoring will be randomized to one of three treatment groups: Surgical Treatment (laparoscopic Nissen fundoplication), Active Medical Treatment (omeprazole and baclofen initially; desipramine for baclofen failures) or Placebo Medical Treatment (omeprazole, placebo baclofen, placebo desipramine). All patients will have quarterly clinic visits for symptom scoring and laboratory testing. At one year, patients will have a final symptom scoring and repeat endoscopy, esophageal manometry and esophageal pH/impedance monitoring. Treatment success will be defined as 50% improvement in the GERD-HRQL score at 12 months. Patients also will complete the Hospital Anxiety and Depression Scale (HADS), Rome III Functional GI Disorders Questionnaire and the Short-Form Health Survey (SF-36) at baseline and one year. The results will be correlated with treatment outcomes.
- Conditions
- GERD
- Being tested
- Nissen fundoplication, baclofen, Desipramine
- Medical subject headings
- Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nissen fundoplicationDevice
laparoscopic antireflux surgery
baclofenDrug
Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals.
The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved.
DesipramineDrug
Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
| Study group | Role | What they receive |
|---|---|---|
| Medical Treatment Group | Other | Omeprazole or Omeprazole + baclofen or Omeprazole + desipramine Receives: Drug: baclofen; Drug: Desipramine |
| Surgical Treatment Group | Other | Laparoscopic nissen fundoplications Receives: Device: Nissen fundoplication |
| Placebo Medical Treatment Group | Other | Omeprazole + placebo Receives: Drug: baclofen; Drug: Desipramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving at Least a 50% Improvement in the Gastroesophageal Reflux Disease Health-related Quality of Life Index (GERD-HRQL) From Baseline to 12 Months
Success; ≥50% improvement in the baseline GERD-HRQL score at 12 months.
Failure; <50% improvement in the baseline GERD-HRQL score at 12 months or:
- For patients randomized to Surgical Treatment: a.<50% improvement in the baseline GERD-HRQL score and/or persistent heartburn of sufficient severity to warrant treatment with any antisecretory medication, antireflux medication or neurotropic medication at any quarterly clinic visit.
- For patients randomized to Active Medical or Placebo Medical Treatment: a.inability to tolerate both study medications or b.For patients treated with desipramine, i.<50% improvement in baseline GERD-HRQL score symptom after at least 10 weeks of treatment with the second drug at any quarterly clinic visit. c.For patients in whom desipramine is contraindicated,i.<50% improvement in baseline GERD-HRQL score symptom after at least 10 weeks of treatment with baclofen or its corresponding placebo at any quarterly clinic visit.
Measured: 12 months
Secondary outcomes (53)
Number of Enrolled Participants With Esophageal Ulceration.
Measured: Screening
Number of Enrolled Participants With Reflux Esophagus.
Measured: Screening
Number of Enrolled Participants With Eosinophilic Esophagitis
Measured: Screening
Number of Enrolled Participants With Active Ulceration of the Stomach and/or Duodenum.
Measured: Screening
Number of Enrolled Participants With Neoplasm of the Esophagus, Stomach or Duodenum
Measured: Screening
Number of Enrolled Participants With Candida Esophagitis.
Measured: Screening
Number of Enrolled Participants With Gastric Outlet Obstruction
Measured: Screening
Number of Enrolled Participants With Achalasia
Measured: Screening
Number of Enrolled Participants With Aperistalsis
Measured: Screening
Number of Enrolled Participants With Distal Esophageal Spasm
Measured: Screening
Number of Enrolled Participants With Nutcracker Esophagus
Measured: Screening
Number of Enrolled Participants With Ineffective Esophageal Motility
Measured: Screening
Number of Enrolled Participants With Rapid Contraction
Measured: Screening
Number of Enrolled Participants With Hypertensive Peristalsis
Measured: Screening
Number of Enrolled Participants With Jackhammer Esophagus
Measured: Screening
Number of Enrolled Participants With Weak Peristalsis I
Measured: Screening
Number of Enrolled Participants With Weak Peristalsis II
Measured: Screening
Number of Enrolled Participants With Anxiety and/or Depression
Measured: Screening
Number of Enrolled Participants With Functional Heartburn
Measured: Screening
Number of Enrolled Participants With Functional Chest Pain of Presumed Esophageal Origin
Measured: Screening
Number of Enrolled Participants With Functional Dysphagia
Measured: Screening
Number of Enrolled Participants With Globus
Measured: Screening
Number of Enrolled Participants With Belching Disorders
Measured: Screening
Number of Enrolled Participants With Chronic Idiopathic Nausea
Measured: Screening
Number of Enrolled Participants With Functional Vomiting
Measured: Screening
Number of Enrolled Participants With Cyclic Vomiting Syndrome
Measured: Screening
Number of Enrolled Participants With Irritable Bowel Syndrome
Measured: Screening
Number of Enrolled Participants With Functional Bloating
Measured: Screening
Number of Enrolled Participants With Functional Diarrhea
Measured: Screening
Number of Enrolled Participants With Unspecified Functional Bowel Disorder
Measured: Screening
Number of Enrolled Participants With Functional Gallbladder Disorder
Measured: Screening
Number of Successful Participants With Anxiety and/or Depression.
Association between anxiety and/or depression (GAD-7 and PHQ-9) and the outcome of medical and surgical treatments (success or failure) will be evaluated.
Measured: 12 months
Number of Successful Participants With Functional Heartburn
Presence of functional heartburn as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Functional Chest Pain of Presumed Esophageal Origin
Presence of functional chest pain of presumed esophageal origin as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Functional Dysphagia
Presence of functional dysphagia as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Globus
Presence of globus as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Belching Disorders
Presence of belching disorders as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Chronic Idiopathic Nausea
Presence of chronic idiopathic nausea as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Functional Vomiting
Presence of functional vomiting as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Cyclic Vomiting Syndrome
Presence of cyclic vomiting syndrome as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Irritable Bowel Syndrome
Presence of irritable bowel syndrome as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Functional Bloating
Presence of functional bloating as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Functional Diarrhea
Presence of functional diarrhea as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Unspecified Functional Bowel Disorder
Presence of unspecified functional bowel disorder as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Participants With Functional Gallbladder Disorder
Presence of functional gallbladder disorder as assessed by the ROME III functional GI disorders questionnaire.
Measured: 12 months
Number of Successful Surgery Participants With Dissection of Distal Esophagus to Obtain at Least 2.5cm of Tension-free, Intra-abdominal Esophagus Performed.
Measured: 12 months
Number of Successful Surgery Participants With Complete Mobilization of the Fundus, to Include All Short Gastric and Posterior Gastric Vessels to the Base of the Left Crus Performed.
Measured: 12 months
Number of Successful Surgery Participants With Closure of the Crura With Non-absorbable Suture to be Snug With a Dilator of at Least 56 French Diameter Performed.
Measured: 12 months
Number of Successful Surgery Participants With Passage of an Esophageal Dilator of at Least 56 French Diameter Performed.
Measured: 12 months
Number of Successful Surgery Participants With Fundoplication Between 1.5 and 2.5cm in Length Performed.
Measured: 12 months
Number of Successful Surgery Participants With Fundoplication Placed Above the Epiphrenic Fat Pad, Using 3 Sutures Performed.
Measured: 12 months
Number of Successful Surgery Participants With Fundoplication Secured to Esophagus With at Least Two Sutures Performed.
Measured: 12 months
Number of Successful Surgery Participants With Fundoplication Floppiness Demonstrated by Passing a Grasper Between Fundoplication and Dilator-filled Esophagus Performed.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study start13 Aug 2012
- Primary completion30 Dec 2016
- Study completion30 Dec 2016
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 GERDStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 366 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Stuart J Spechler, MD, Study chair, VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265550
- Sponsor's protocol ID
- 573
- Status last verified
- Jan 2020
- First submitted
- 21 Dec 2010
- Last updated
- 22 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Spechler SJ, Hunter JG, Jones KM, Lee R, Smith BR, Mashimo H, Sanchez VM, Dunbar KB, Pham TH, Murthy UK, Kim T, Jackson CS, Wallen JM, von Rosenvinge EC, Pearl JP, Laine L, Kim AW, Kaz AM, Tatum RP, Gellad ZF, Lagoo-Deenadayalan S, Rubenstein JH, Ghaferi AA, Lo WK, Fernando RS, Chan BS, Paski SC, Provenzale D, Castell DO, Lieberman D, Souza RF, Chey WD, Warren SR, Davis-Karim A, Melton SD, Genta RM, Serpi T, Biswas K, Huang GD. Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn. N Engl J Med. 2019 Oct 17;381(16):1513-1523. doi: 10.1056/NEJMoa1811424.
PubMed 31618539
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CSP #573 - A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors
- ClinicalTrials.gov ID
- NCT01265550
- Acronym / sponsor ID
- 573
- Conditions
- GERD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 366 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 13 Aug 2012 (actual)
- Primary completion
- 30 Dec 2016 (actual)
- Study completion
- 30 Dec 2016 (actual)
- First posted
- 23 Dec 2010 (estimated)
- Results
- Posted 26 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Gastroesophageal reflux disease (GERD), which affects at least 20% of adult Americans, may be especially common and severe in Veteran patients. Proton pump inhibitors (PPIs), which block gastric acid production, are the most effective medications for GERD, and the VA spends more than $177 million each year on outpatient PPI prescriptions. PPIs do not prevent the reflux of non-acidic material and do not completely eliminate esophageal acid exposure, however, and bothersome GERD symptoms persist in approximately 40% of patients treated with PPIs. Recent studies using the new technique of esophageal pH/ impedance monitoring, which detects the reflux of both acidic and non-acidic materials, have shown that PPI-resistant GERD symptoms correlate with episodes of reflux (acidic and/or non-acidic) in approximately one-half of patients. For those patients, an antireflux operation might relieve symptoms and obviate the expense of ineffective PPI therapy, but the efficacy of modern, laparoscopic fundoplication in this regard is not clear. For patients with PPI-resistant GERD symptoms, furthermore, the efficacy of medications that that can prevent gastroesophageal reflux (e.g. baclofen) or diminish pain of esophageal origin (e.g. neurotropic agents like desipramine) also is not clear. Study Hypothesis: Laparoscopic antireflux surgery (Nissen fundoplication) is superior to medical therapy (PPIs plus baclofen and desipramine) for GERD patients who, while on PPIs, have persistent episodes of heartburn that are associated with reflux episodes or with abnormal esophageal acid exposure by esophageal pH/impedance monitoring.
Study Goals: The primary goal is to compare the efficacy of laparoscopic Nissen fundoplication and medical therapy (PPIs plus baclofen and desipramine) for GERD patients who, while on PPIs, have persistent episodes of heartburn that are associated with reflux episodes or with abnormal esophageal acid exposure by esophageal pH/impedance monitoring, and to compare the efficacy of each therapy with placebo. Secondary goals are: 1) To determine the frequency with which non-GERD disorders underlie "PPI failure," 2) To determine the frequency of functional gastrointestinal symptoms, anxiety and depression in patients who have persistent heartburn while on PPIs, 3) To determine whether functional gastrointestinal symptoms, anxiety and depression is associated with the outcomes of medical and surgical therapies, and 4) To determine whether the outcome of Nissen fundoplication is associated with adherence to technical aspects of the operation.
Study Design: Up to 16 VA medical centers, there will be a 30-month recruitment period to enroll 108 patients with heartburn that is refractory to PPI therapy. Patients will have their baseline GERD symptoms scored using the GERD Health-Related Quality of Life (GERD-HRQL) index, and will have endoscopy, esophageal manometry and esophageal pH/impedance monitoring while on PPI therapy. Patients who have episodes of heartburn that are associated with reflux episodes or with abnormal esophageal acid exposure by esophageal pH/impedance monitoring will be randomized to one of three treatment groups: Surgical Treatment (laparoscopic Nissen fundoplication), Active Medical Treatment (omeprazole and baclofen initially; desipramine for baclofen failures) or Placebo Medical Treatment (omeprazole, placebo baclofen, placebo desipramine). All patients will have quarterly clinic visits for symptom scoring and laboratory testing. At one year, patients will have a final symptom scoring and repeat endoscopy, esophageal manometry and esophageal pH/impedance monitoring. Treatment success will be defined as 50% improvement in the GERD-HRQL score at 12 months. Patients also will complete the Hospital Anxiety and Depression Scale (HADS), Rome III Functional GI Disorders Questionnaire and the Short-Form Health Survey (SF-36) at baseline and one year. The results will be correlated with treatment outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Medical Treatment Group | Other | Drug: baclofen, Drug: DesipramineOmeprazole or Omeprazole + baclofen or Omeprazole + desipramine |
| Surgical Treatment Group | Other | Device: Nissen fundoplicationLaparoscopic nissen fundoplications |
| Placebo Medical Treatment Group | Other | Drug: baclofen, Drug: DesipramineOmeprazole + placebo |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age 18-70 years
- History of heartburn (defined as a burning sensation in the retrosternal area of the chest) that is refractory to antisecretory medications
- Initial GERD-HRQL:
- GERD-HRQL after two weeks of treatment with omeprazole:
- Either or both of the following by baseline esophageal pH/multichannel intraluminal impedance (MII) monitoring in patients on omeprazole 20 mg two times a day (BID):
Key exclusion criteria (40 listed)
- Patients who do not have heartburn, defined as a burning sensation in the chest
- Patients unwilling or unable to provide informed consent
- Pregnancy or women unwilling to use effective contraception
- Age <18 or >70 years
- History of surgery on the stomach or esophagus
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 |
|---|---|---|
| Nissen fundoplicationlaparoscopic antireflux surgery | Device | Surgical Treatment Group |
| baclofenBaclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. | Drug | Medical Treatment Group, Placebo Medical Treatment Group |
| DesipramineDose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit. | Drug | Medical Treatment Group, Placebo Medical Treatment Group |
Primary outcome
Number of Participants Achieving at Least a 50% Improvement in the Gastroesophageal Reflux Disease Health-related Quality of Life Index (GERD-HRQL) From Baseline to 12 Months
Time frame: 12 months
Success; ≥50% improvement in the baseline GERD-HRQL score at 12 months. Failure; <50% improvement in the baseline GERD-HRQL score at 12 months or: 1. For patients randomized to Surgical Treatment: a.<50% improvement in the baseline GERD-HRQL score and/or persistent heartburn of sufficient severity to warrant treatment with any antisecretory medication, antireflux medication or neurotropic medication at any quarterly clinic visit. 2. For patients randomized to Active Medical or Placebo Medical Treatment: a.inability to tolerate both study medications or b.For patients treated with desipramine, i.<50% improvement in baseline GERD-HRQL score symptom after at least 10 weeks of treatment with the second drug at any quarterly clinic visit. c.For patients in whom desipramine is contraindicated,i.<50% improvement in baseline GERD-HRQL score symptom after at least 10 weeks of treatment with baclofen or its corresponding placebo at any quarterly clinic visit.
53 secondary outcomes
Number of Enrolled Participants With Esophageal Ulceration.
Time frame: Screening
Number of Enrolled Participants With Reflux Esophagus.
Time frame: Screening
Number of Enrolled Participants With Eosinophilic Esophagitis
Time frame: Screening
Number of Enrolled Participants With Active Ulceration of the Stomach and/or Duodenum.
Time frame: Screening
Number of Enrolled Participants With Neoplasm of the Esophagus, Stomach or Duodenum
Time frame: Screening
Number of Enrolled Participants With Candida Esophagitis.
Time frame: Screening
Number of Enrolled Participants With Gastric Outlet Obstruction
Time frame: Screening
Number of Enrolled Participants With Achalasia
Time frame: Screening
Number of Enrolled Participants With Aperistalsis
Time frame: Screening
Number of Enrolled Participants With Distal Esophageal Spasm
Time frame: Screening
Number of Enrolled Participants With Nutcracker Esophagus
Time frame: Screening
Number of Enrolled Participants With Ineffective Esophageal Motility
Time frame: Screening
Number of Enrolled Participants With Rapid Contraction
Time frame: Screening
Number of Enrolled Participants With Hypertensive Peristalsis
Time frame: Screening
Number of Enrolled Participants With Jackhammer Esophagus
Time frame: Screening
Number of Enrolled Participants With Weak Peristalsis I
Time frame: Screening
Number of Enrolled Participants With Weak Peristalsis II
Time frame: Screening
Number of Enrolled Participants With Anxiety and/or Depression
Time frame: Screening
Number of Enrolled Participants With Functional Heartburn
Time frame: Screening
Number of Enrolled Participants With Functional Chest Pain of Presumed Esophageal Origin
Time frame: Screening
Number of Enrolled Participants With Functional Dysphagia
Time frame: Screening
Number of Enrolled Participants With Globus
Time frame: Screening
Number of Enrolled Participants With Belching Disorders
Time frame: Screening
Number of Enrolled Participants With Chronic Idiopathic Nausea
Time frame: Screening
Number of Enrolled Participants With Functional Vomiting
Time frame: Screening
Number of Enrolled Participants With Cyclic Vomiting Syndrome
Time frame: Screening
Number of Enrolled Participants With Irritable Bowel Syndrome
Time frame: Screening
Number of Enrolled Participants With Functional Bloating
Time frame: Screening
Number of Enrolled Participants With Functional Diarrhea
Time frame: Screening
Number of Enrolled Participants With Unspecified Functional Bowel Disorder
Time frame: Screening
Number of Enrolled Participants With Functional Gallbladder Disorder
Time frame: Screening
Number of Successful Participants With Anxiety and/or Depression.
Time frame: 12 months
Number of Successful Participants With Functional Heartburn
Time frame: 12 months
Number of Successful Participants With Functional Chest Pain of Presumed Esophageal Origin
Time frame: 12 months
Number of Successful Participants With Functional Dysphagia
Time frame: 12 months
Number of Successful Participants With Globus
Time frame: 12 months
Number of Successful Participants With Belching Disorders
Time frame: 12 months
Number of Successful Participants With Chronic Idiopathic Nausea
Time frame: 12 months
Number of Successful Participants With Functional Vomiting
Time frame: 12 months
Number of Successful Participants With Cyclic Vomiting Syndrome
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31618539Spechler SJ, Hunter JG, Jones KM, Lee R, Smith BR, Mashimo H, Sanchez VM, Dunbar KB, Pham TH, Murthy UK, Kim T, Jackson CS, Wallen JM, von Rosenvinge EC, Pearl JP, Laine L, Kim AW, Kaz AM, Tatum RP, Gellad ZF, Lagoo-Deenadayalan S, Rubenstein JH, Ghaferi AA, Lo WK, Fernando RS, Chan BS, Paski SC, Provenzale D, Castell DO, Lieberman D, Souza RF, Chey WD, Warren SR, Davis-Karim A, Melton SD, Genta RM, Serpi T, Biswas K, Huang GD. Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn. N Engl J Med. 2019 Oct 17;381(16):1513-1523. doi: 10.1056/NEJMoa1811424.
- 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.
Stuart J Spechler, MD study chair
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nissen fundoplication, baclofen and Desipramine in people with GERD, run by VA Office of Research and Development at 15 sites 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 9 inclusion and 40 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: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 26 Feb 2018). 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?
Number of Participants Achieving at Least a 50% Improvement in the Gastroesophageal Reflux Disease Health-related Quality of Life Index (GERD-HRQL) From Baseline to 12 Months (time frame: 12 months). 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 NCT01265550, 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 22 Jan 2020.