introducing linx to practice
DESCRIPTION
Presentation given as part of Best Practices Meeting during 2012 DDW meeting in San DiegoTRANSCRIPT
LINX® Reflux Management System: Best Practices Meeting
Friday, May18, 2012
C. Daniel Smith, MDChair, Department of Surgery
Surgeon-in-Chief
Mayo Clinic in Florida
Establishing the LINX® System as a Surgical Offering
Disclosure
- Co-PI for one of the sites who participated in the Pivotal Trial
- Advisor/consultant to Torax for preparation of the presentation to FDA
- Joined company for presentation to FDA
- Paid consultant to company helping with safe and successful introduction of Linx to care of GERD patients
Goals for This Portion of Discussion
- I’m not going to tell anyone in audience anything that they don’t already know
- Offer perspective on current surgical treatment for GERD (Nissen fundoplication)
- Where would Linx fit in surgical practice
- What is the Linx patient
- Propose principles for use in our practices
Fundoplication
- Great operation
- Select patients do very well
- Superior to PPIs
- Significant positive impact on natural history of GERD
- Multiple studies have confirmed its effectiveness and role in treatment of GERD
Current Treatment Options for GERD N
o. G
ERD
Pati
ents
Severity of Symptoms and Dissatisfaction Mild Severe
PPI TherapyPPI Therapy
FundoplicationSurgery
FundoplicationSurgery
Fundoplication
- Use of fundoplication for GERD has peaked, use has been slowly declining
- GIs have largely stopped referring patients except for desperate or complicated cases
- Most cases are done for complicated conditions (redo, large hiatal hernia, Barretts, severe refractory GERD
- PPIs remain treatment of choice for all but the most severe cases of GERD
Fundoplication – Why Not
- Multifactorial
- Technical failures – inconsistent and questionable outcomes
- Lack of standardized approach/technique
- Inconsistent use – patients still have fundoplication performed without objective confirmation fo GERD
- Patients are afraid of the operation – troubling side-effects of gas bloat and excess flatus or perception that failure rate is 50%
- GIs refuse to refer – all of the above and/or strong belief that it is a bad operation
- Competing treatments – primarily PPIs, some endolumenal approaches
Two Predictors of Surgical Outcome
Patient Selection Operative Technique
• Patients without objective confirmation of GERD
• Patients who fail to respond to PPIs
• Patients with BMI >35
• Atypical symptoms?
• Occasional antireflux surgeon
• Patient selection can be tricky
• Defining the typical GERD patient has been difficult
• 2 stitch, three stitch, four stitch• Esophageal stitch, how many and
location• Pledgets for wrap or crural repair• Divide short gastrics or not• Anchor wrap to diaphragm/crura• Extensive esophageal mobilization• Calibrate wrap and to what size• Occasional antireflux surgeon• Tricky operation• Not everyone can get good
outcomes
Fundoplication
Current Treatment Options for GERD N
o. G
ERD
Pati
ents
Severity of Symptoms and Dissatisfaction Mild Severe
PPI Therapy
FundoplicationSurgery
Therapy Gap
No standard treatment for Gap patients
Targeted Linx population
Pivotal Trial
Key Outcomes
Summary of Efficacy Endpoints
Percent Successful (95% Binomial Exact Confidence Limits)
0 10 20 30 40 50 60 70 80 90 100
Secondary: PPI ≥ 50% reduction in daily PPI use
Secondary: GERD ≥ 50% reduction in GERD-HRQL
Primary: pH Normalization or ≥ 50% reduction
64% (:54, 73%)
92% (85, 97%)
93% (86, 97%)
Efficacy Endpoints by Baseline Hernia Assessment (≤3 cm)
Primary Efficacy Endpoint Component No Hernia All Patients
Normalization (pH<4.5%) 67% (29/43) 58.3% (56/96)> 50% reduction from baseline 77% (33/43) 63.5% (61/96)Either normalization or > 50% reduction 79% (34/43) 66.7% (64/96)
PPI Free DaysAs of Last Follow-Up
0
100
200
300
400
500
600
700
800
900
PPI F
ree
Day
s
Minimal Side Effects
Ability to Belch• 99% of patients throughout study
period
Inability to Vomit• 0% at 12 months• 1% at 24 months
Note: As actively queried by Foregut Questionnaire
Reduced Gas Bloat
Baseline 12 Month Post LINX 24 Month Post LINX0
20
40
60
80
100
Severity of Gas BloatFREQUENTLY CONTINOUSLY
Pe
rce
nt
of
Pa
tien
ts R
ep
ort
ing
Note: As actively queried by Foregut Questionnaire
Overall Acceptable Safety Risk
144 patients implanted between 2-4 years No deaths No intra-operative complications No device failures No device erosions or migrations
Serious Adverse Events
6% (8/144) No late onset (>1 year)
The Successful LINX Patient
Post-LINX% of Pts 2 Years
8%
2%
2%
1%
1%
12%
11%
Baseline% of Pts Characteristic
100% Daily PPI dependence
70% Reflux affecting their sleep on a daily basis
76% Reflux affecting their food tolerances on a daily basis
57% Moderate or severe regurgitation including aspirations
55% Severe heartburn affecting their daily life
51% Experiencing extra esophageal symptoms in addition to heartburn and/or regurgitation
40% Esophagitis
How Were Good Results Achieved
• Rigorous adherence to patient selection and standardized surgical technique (arguably, even tighter adherence to standardized surgical technique would have improved outcomes even further)
Hernia at Baseline NpH
Endpoint Success
GERD-HRQLEndpoint Success
PPI UseEndpoint Success
None 44 77% 89% 91%Yes – repaired 30 67% 100% 97%
Yes – not repaired 26 39% 89% 92%
pH Endpoint Success 95% CINo hernia or hernia repaired 73.0% (54 / 74) 61.4, 82.7%
Two Predictors of Surgical Outcome
Patient Selection Operative Technique
• Tight control on patient selection
• Don’t go after extended inclusion criteria patients
• Work closely with GI to assure full diagnostic work-up and consistent patient selection
• Consistent patient instructions to establish expectations (dysphagia is common, diet progression
• Device that results in predictable response/performance
• Standard technique for placement
• If any question of hiatal defect, approximate crura with stitch(es)
LINX
Defining the LINX® Patient
Key Pivotal IDE Eligibility Criteria
Inclusion
Age 18-75 years Typical GERD symptoms >6 months Pathologic GERD – (esophageal pH<4 for >4.5% of time) Daily PPI use Symptomatic improvement on PPIs
Exclusion
Hiatal hernia (>3cm) Esophagitis Grade C or D (LA classification) Barrett’s esophagus Esophageal motility disorder
Patient Selection Per Labeling
INDICATION
The LINX Reflux Management System is indicated for patients
diagnosed with GERD as defined by abnormal pH testing, who
continue to have chronic GERD symptoms despite
maximum medical therapy for the treatment of reflux.
Patient Selection Per Labeling
PRECAUTIONS 1. Hiatal hernia >3 cm
2. Barrett’s esophagus
3. Esophagitis grade C or D
4. Electrical implants or metallic abdominal implants
5. Major motility disorders
6. Scleroderma
7. Esophageal or gastric cancer
8. Dysphagia greater than once per week within the last 3 months
9. Esophageal or gastric surgery or endoscopic intervention
10. Distal amplitude <35 mmHg or <70% peristaltic sequences
11. Esophageal stricture or gross anatomic abnormalities
12. Esophageal or gastric varices
13. Lactating, pregnant or plan to become pregnant
14. Morbid obesity (BMI >35)
15. Age <21 years
These PRECAUTIONS are
based on the inclusion/exclusion
criteria of the pivotal study.
Patients outside of these
PRECAUTIONS have not been studied.
Extended Criteria Use
• Linx in hiatal hernia > 3 cm
• Linx in Barretts
• Linx in morbid obesity (BMI > 35)
• Linx with sleeve gastrectomy
Defining the LINX® PatientExamples
Examples
• 45 year old male• Heartburn is primary symptom• Double dose PPI for last 3 years• pH < 4.5 10%• Normal esophageal motility• Normal EGD• 2 cm sliding hiatal hernia• Completely satisfied on current PPI regimen
• LINX Patient?
Examples
• 24 year old female• Chest pain is primary symptom• Single dose PPI for last 6 months• pH < 4.5 - 6%• Normal esophageal motility• Normal EGD• Carries diagnosis of fibromyalgia• Absolutely no improvement in GERD symptoms on
PPIs
• LINX Patient?
Examples
• 51 year old male• Heartburn is primary symptom• Single dose PPI for last 10 years• pH < 4.5 - 11%• Normal esophageal motility• Normal EGD• PPI controls heartburn symptom• Recent onset of night time regurgitation• 3 cm hiatal hernia
• LINX Patient?
Examples
• 58 year old female• Heartburn is primary symptom• Double dose PPI for last 10 years• pH – Bravo has failed twice and can’t tolerate
catheter-based pH• Normal esophageal motility• Normal EGD• PPI controls most of symptoms, some breakthrough,
concerned about osteoporosis and reports of hip fracture when on PPIs
• No hiatal hernia
• LINX Patient?
Examples
• 72 year old male• Chest pain and regurgitation are primary symptoms• Double dose PPI for last 15 years• pH < 4.5 – 8%• Normal esophageal motility• EGD with irregular SCJ – biopsy with non-dysplastic
Barretts• History of short segment Barretts with – Halo
ablation 6 months earlier• PPI does not control symptoms • 3 hiatal hernia
• LINX Patient?
Examples
• 18 year old male• Chest pain and heartburn• Single dose PPI for last 2 years• pH < 4.5 – 8%• Normal esophageal motility• EGD with eosinophilic esophagitis• PPI does not control symptoms • No hiatal hernia
• LINX Patient?
Examples
• 23 year old female• Hoarseness and chronic cough are primary
symptoms• Double dose PPI for last 5 years• pH < 4.5 – 2% on PPIs, Impedence pH with non-acid
reflux episodes without correlation to symptoms• Esophageal motility with disordered peristalsis, but
70% peristaltic and body pressure of 35 mm Hg• EGD normal• PPI helps some• No hiatal hernia
• LINX Patient?
Summary / Principles
• Linx is a safe and effective tool for the management of GERD
• In carefully selected patients outcomes are excellent and reproducible across a variety of settings
• The maintenance of these good outcomes will be critical to gaining acceptance and reimbursement for this treatment option
• Tight adherence to strict work-up, selection criteria and operative technique is critical to achieving the consistent and good outcomes achieved in the Pivotal Trial and needed for the ongoing success of this offering
Summary / Principles
• We should agree as thought leaders in the field to adhere to these principles in offering Linx to our patients
• Extended inclusion criteria use should be done through agreed upon study so as to segregate data and outcomes
• if we do this we can help assure the advancement of our field through responsible introduction of new techniques to clinical practice
Discussion