Clinical trial: radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients

Alimentary Pharmacology & Therapeutics

Clinical trial: radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients E. CORON*, V. SEBILLE , G. CADIOTà, F. ZERBIB§, P. DUCROTTE–, F. DUCROT**, P. POUDEROUX  , J. ARTSàà, M. LE RHUN*, T. PICHE§§, S. BRULEY DE S VARANNES*,–– & J. P. GALMICHE*,–– CONSORTIUM DE RECHERCHE INDE´ PENDANT SUR LE TRAITEME NT ET L’EXPLORATION DU REFLUX GASTRO-OESOPHAGIEN ET DE L’ENDOBRACHYOESOPHAGE (CRITERE)

*Institut des Maladies de l’Appareil Digestif, CHU Hoˆtel-Dieu, Nantes;  De´partement de Biostatistiques, CHU Hoˆtel-Dieu, Nantes; àService d’He´patogastroente´rologie, CHU Robert Debre´, Reims; §Service d’He´patogastroente´rologie, Hoˆpital St-Andre´, Bordeaux; –De´partement d’He´patogastroente´rologie, CHU Charles Nicolle, Rouen; **Clinique des Ormeaux-Vauban Le Havre, Le Havre;   Service d’He´patogastroente´rologie, CH Nıˆmes; ààAZ Sint-Lucas, Bruges; §§Service d’He´patogastroente´rologie, CHU, Nice; ––CIC-INSERM, CHU Hoˆtel-Dieu, Nantes, France Correspondence to: Dr J. P. Galmiche, Service d’He´patoGastroente´rologie, Institut des Maladies de l’Appareil Digestif Nantes, CHU Nantes, F-44093 France; Institut National de la Sante´ et de la Recherche Me´dicale, U913, CIC 0004, Nantes, F-44093 France. E-mail: jeanpaul.galmiche@ chu-nantes.fr

Publication data Submitted 5 June 2008 First decision 18 June 2008 Resubmitted 26 June 2008 Accepted 27 June 2008 Epub Accepted Article 4 July 2008

SUMMARY Background Radiofrequency (RF) energy delivery is an endoscopic procedure developed for the treatment of gastro-oesophageal reflux disease. Aim To compare RF and a proton pump inhibitor strategy (PPI) in PPI-dependent patients by carrying out a prospective, randomized trial. Methods Patients with PPI-dependent typical reflux symptoms were randomly allocated to either RF or PPI regimen alone. The primary endpoint, evaluated at 6-month, was defined as the possibility for the patient to stop or to decrease PPI use to 3 cm and ⁄ or with dysplasia and ⁄ or previously treated; (ii) presence of hiatus hernia >3 cm; (iii) presence of oesophagitis grade C or D in LA classification; (iv) presence of oesophageal stricture or achalasia; (v) history of oesophageal or gastric surgery; (vi) presence of gastric or oesophageal varices; (vii) presence of a cardiac pacemaker or any other implanted electro-medical device; (viii) impossibility to stop an anticoagulant therapy or severe coagulopathy; (ix) any contraindication to general anaesthesia; (x) life threatening disorders with a life expectancy of 60 g ⁄ day); (xii) morbid obesity (BMI over 35); (xiii) patients whose symptoms are adequately relieved with half-dose PPI regimen or intermittent acid suppression; and (xiv) inability to understand the study protocol or refusal to give informed consent.

Run-in phase (Figure 1a). During a 6-to-12 week run-in phase, PPI dependent patients underwent a prerandomization work-up (Figure 1) to determine frequency and intensity of typical GERD symptoms, HR-QOL and PPI needs and to perform 24-h oesophageal pH monitoring, oesophageal manometry and upper GI endoscopy at baseline (if these examinations had not been performed within the previous 6 months). In particular, baseline PPI needs were determined carefully according to a standardized protocol. Patients were asked to take their PPIs daily and the effective

dose (ED) was defined as the dose allowing adequate control of symptoms during 3 weeks. Adequate control was defined as 5 min* Duration of reflux episodes (s)* Symptom index (%)* LOS pressure (mmHg)* Endoscopy Oesophagitis (%) Oesophagitis A ⁄ B Short Barrett (%) Hiatus hernia £3 cm (%)

RF (n = 23)

P-value

50  10 16 ⁄ 7 26  3 41  22

0.37 0.97 0.51 0.57

14 (61) 10.0 (2–44) 5 (22)

0.78 0.28 1.00

1.3  0.6 1.2  0.5 1.5  0.8

1.6  0.7 1.6  1.0 1.4  0.7

0.12 0.10 0.48

46  7 46  9

49  7 45  12

0.19 0.71

       

20 22 22 24 20 22 27 25

0.94 0.87 0.95 0.82 0.60 0.54 0.30 0.43

17 ⁄ 3  10.7 6  49  23 8

23 ⁄ 0 12.2  7.1 75 69  23 89  12 13  8

0.09 0.43 0.79 0.27 0.19 0.89

5 (25) 3⁄2 1 (5) 9 (45)

8 (35) 4⁄4 3 (13) 7 (30)

0.49 – 0.61 0.32

47  14 14 ⁄ 6 27  4 46  25 13 (65) 9.5 (1–25) 4 (20)

68 70 64 68 60 65 71 63

12.1 6 82 75 14

       

16 23 34 22 20 18 25 24

67 71 67 70 63 68 62 57

Control group: proton pump inhibitor regimen alone; RF: Radiofrequency energy delivery; LOS: lower oesophageal sphincter. * Values are expressed as mean  s.d.   On therapy. à A 24-h oesophageal acid exposure time equal to or higher than 4% was considered pathological.

Primary endpoint At 6 months, ITT analysis (whereby all missing values in both groups were considered as failures to stop or decrease their PPI use to