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Effect of Helicobacter pylori eradication on recurrence of bleeding duodenal ulcer and dyspeptic symptoms: A two-year prospective study
high eradication rate could be achievedwithout the development of resistance.Furthermore, CYP2C19 genotype status is associated with cure rate of H.pylori infection. (Subject and methods) a total 100 subjects with H.pyloriwere randomly divided into four groups. (i) OAC regimen (n=25): omeprazole20rag o.d,, AMPG 500 mg t.d.s., CAM 200rag t.d.s., for 7day; (if) LAG regimen (n =25): tansoprazole30 mg o.d., AMPG500 mg t.d.s., CAM 200mg t.d.s., for 7day; (iii) RAC regimen (n=25): RPZ 10 mg o.d., AMPC 500 mg t.d.s, CAM 2OOmgt.d.s., for 7days; (iiii) RA regimen (n =25): RPZ 20 rng o.d. AMPC 5OOmgq.d.s, for 14days.The status of H.pylori infection was determined using culture and histology. Cure was defined as no evidence of H.pylori infection 8 weeks after completion of treatment. Susceptibility to AMPC and CAM was determined using agar plating dilution method before and after treatment.GYP2C19 genotybe was determined by PCR-RFLP methods. (Result) Intention to treat based cure rates for OAG, LAC, RAC, RA regimens were 76.0%, 68.0%, 76.0% and 80.0%, respectively,and per protocol basedcure rates of these regimens were 82.6%, 73.9%, 79.2% and 83.3%, respectively. Cure rate was 69.7% (25/33) in rapid extensive metabolizer of CYP2C19 (REM), 80.9% (38/47) in hetero extensivemetabolizer(HEM) and 84.6%(11/13) in poor metabolizer(PM) in all. Cure rates for REM, HEM and PM were 66.7%, 100% and 75% in OAC regimen, 77.8%, 66.7% and 100% in LAC regimen, 75%, 76.9% and 100% in RAC regimen,85.7%, 80.3% and 80% in RA regimen respectively.No significant changewas noted in any regimens. Number of patients with CAM resistant strain after treatment in OAC, LAG, RAG, and RA regimens was one, four, two and none respectively. No patient with AMPG resistant strain was noted before and after treatment. (Conclusion) Two-weeks dual therapy of RPZ and AMPG was effective for the eradication of H.pylori without increase of CAMresistant strain.
regimen
LCD
n PP (ITT)
10 O % (0 %)
LCA 19 41% (37 %)
LCT-Gd
LCT-7d
24 87 % (83 %)
38 92 % (87 %)
2974 High Efficacy of Ranitidine Bismuth Citrate, Amoxicillin, Clarithramycin and Metronidazole Twice Daily for Only Five Days in Helicobacter pylori Eradication J P. Gisbert, La Princess Univ Hosp, Madrid Spain; S Marcus, J L Gisbert, J Canter(}, J M Pajares AIM: The combination of a proton pump inhibitor (PPI) or ranitidine-bismuth citrate (Rbc) and two antibiotics during 7 to 10 days are, at present, the treatments of choice in H. pylori eradication. However, therapies for less than 7 days have been scarcely evaluatedand it is unknown whether the length of treatment can be shortened,without a lost of efficacy, if three instead of two antibiotics are used. The aim of our study was to evaluatethe efficacy of Rbc plus three antibiotics for only five days in H. pylori eradication. METHODS:We prospectively studied 100 patients (35% duodenal ulcer, 65% functional dyspepsia) infected by H. pylori. At endoscopy,biopsies were obtained for histological study and rapid ureasetest, and a ~aCurea breath test was carded out. Urea breath test was repeatedfour weeks after completing eradication treatment with Rbc (400 mg b.i.d.), amoxicillin (1 g h.i.d.), clarithromycin (500 mg b.i.d.), and metronidazole (500 mg b.i.d.). All drugs were administered together after breakfast and dinner and for five days only, and no treatment was administered thereaffer. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. RESULTS: In 98 out of the 100 patients, H. pylori eradication success or failure was assessedafter therapy (two patients were lost from follow-up). All but two of these 98 patients took all the medications (two patients stopped treatment on the third day due to nausea/vomiting). Per protocol eradication was achievedin 88•96 (92%; 95% CI, 84-96%) and in 88/100 (88%; 82-94%) by intention-to-treat. Therapy was more effective in patients with duodenal ulcer than in those with functional dyspepsia [100% vs. 82% by intention-to-treat; p
2972 Effect of Helicohacter pylori Eradication on Recurrence of Bleeding Duodenal Ulcer and Dyspeptic Symptoms:A Two-Year Prospective Study Silvano Loperfido, Rita Priora, Fabio Monica, Helena Heras Salvat, GastroenterologyUnit, Hosp ULSS 9, Treviso Italy; Luigi Angelillis, Luisa Maifreni, EmergencyMedicine Dept, Hosp ULSS 9, Treviso Italy Background Helicobacterpylorieradication reducesthe recurrencesof peptic ulcer and seems to preventrebleeding.Little is known regardingdyspepticand reflux symptoms after eradication in patients with complicated ulcer. Aims To determine the recurrence rate of ulcer and rebleeding after eradication in patients who had bled from a duodenal ulcer. To evaluate dyspeptic and reflux symptoms on long-term follow up. Methods From January 1996 to September 1998 50 consecutive H.pylori positive patients admitted for bleeding duodenal ulcer and undergoing conservative treatment were treated, as soon as oral route was reestablished, with a dual eradication regimen: ranitidine bismuth citrate 400 rng b.i.d, for four weeks, plus cladthromycin 500 mg b.i.d, for the first two weeks. Male/Femaleratio was 5.2, mean age 54 years, 25 had a history of peptic ulcer, and 10 had experiencedprevious digestive hemorrhage. Healing of the ulcer and H.pylori status were evaluated endoscopically eight weeks after initiation of therapy. Healedand eradicated patients entered a clinical and endoscopic follow up study with exclusion of NSAIDs,anti-pleteletand antisecretorydrugs. Results Forty six patients followed the protocol and were fully compliant. Eradication was achieved in 39 (78% on intention to treat analysis,85% per protocol). Thirty eight healedand eradicated patients entered the follow up study. After two years, H.pylori infection had recurred in one patient and duodenal ulcer in one H.pylori negative asymptomatic subject (2.6%). None experiencedrebleeding.Beforetreatment 12 of 38 patients complained of epigastdc pain and 7 of reflux symptoms, white B had both symptoms, After two years, four patients (liP/o) complained of mild epigastric pain, two of whom endoscopicallyshowed antral or duodenal erosions; nine patients (24%) complained of reflux symtoms, two of whom had endoscopic evidenceof esophagitis.Two other patientswith mild esophagitiswere asymptomatic.Conclusions 1) Successful H.pylori eradication prevented rehleeding from duodenal ulcer in 38 patients on follow up; 2) The two-year recurrence rate of non complicated ulcer and the reinfection rate were both 2.6%; 3) Dyspeptic symptoms, most of reflux-like type, with rare evidence of gastroduodenalerosions or esophagitis, persisted, recurred or appearedex novo in a third of patients; 4) In three asymptomatic subjects, endoscopy disclosed peptic ulcer in one and esophagitis in the other two.
2975 Curing Ulcer, Relieving Symptoms? K D. Bardhan, Pierre J. Willemse, Darren Morton, Chdstine Royston, Pamela Morris, Mary Thompson, Anne Rowland, Caroline Shaw, Hilary Allen, District Gen Hosp, Rutherham United Kingdom; Peter Roberts, Alex Godwood, Glaxo-WellcomeResearch & Development, Uxbridge United Kingdom Introduction & Aim We compared omeprazole-basedand ranitidine bismuth citrate(RBC)based H.pylori triple therapy, of which relatively little is known, assessed long-term (ly) outcome and the impact of eradication on subsequent symptoms. Method Patients with endoscopy-provenhealedDU or GU and positive rapid ureasebreathtest (UBT) were randomly allocated to receive one week twice daily RBC 400mg + metronidazole(MET) 4OOmgwith either clarithromycin 500rag (RMG), tetracycline 4OOmg(RMT) or amoxycillin lg (RMA), or omeprazole 20mg + amoxycillin lg + MET 4OOmg (DAM). Antibiotic susceptibility was assessed by disc diffusion. Eradication = negativeUBT at 8 weeks. Results (seeTable) Mean dyspepsia scores: baseline 6.4, eradication (8w,12m) 2.1, 1.9; failed eradication, 2.4, 1.6. During ly follow up after eradication (n=190), 34% required t-12RAor PPI (2_/3for preexisting reflux). Endoscopyat ly in 109/129 followed off treatment showed lesions in 30% (15 with newly developed esopbegitis, only 1 with DU) but with little or no symptoms. Discussion 1. RMGgavebetter results both at 8w & ly hut differences narrowedby ly and were about l/5th lower. 2. Eradicationrates were lower than in our previousstudies, unexplainedby antibiotic resistance alone. 3. UBT at ty may prove a better marker of treatment efficacy. 4. Symptom scores diminished at 8w, remainedlow and were similar with or without eradication. 5. Pre-existingreflux was the main reasonfor restarting H2RNPPI. 6. Peptic ulcer was cured but new esophagitis, mainly silent, developedin 14%. Conclusion RMC & DAM are similarly effective but eradication rates are much less at ly than at 8w. Reductionof symptoms seems independent of eradication. This work was supported by GlaxoWellcome.
2973 The Feasibility Of Once - Daily - Dosing H.Pylori Eradication Therapy Rodolfo E A Seelis, Gastroenterology,Aachen Germany; Werner Dohmen, Gen Medicine, Aachen Germany Background:Attempting to improve patientscompliancewe recentlyhavetried to pay attention to more innovative H.pylori (Hp) therapies. Our objective of this study was to investigate a new once-daily-dosing (qd) approach for Hp-eradication, Method: Open label, prospective, community based investigation of 4 different Hp-tdple-tberapies.A fixed combination of 30 mg lansoprazole(L) qd together with 500rag of the new sustained releaseformula of clarithromycin UD (C) qd was combined with one of the following antibiotics: 0.2 g doxycyclin (D) qd for 7 days (LOB-regimen); 2,0 g amoxycillin (A) qd for 7 days (LCA); 2.0 g tinidazole (T) qd for 6 days (LCT-6d); 1.0 g tinidazole (T) qd for 7 days (LCT-7d). Additionally, every patient once received one pretherapeutic dose of 30 mg lansoprazotethe evening before starting treatment. Hp-therapies yielding low eradication rates (Hp-x), as assessed by urease-test, histology and Hp-cuiture were discontinued quickly, those yielding Hp-x > 90 % had to be proven by at least n > 30 treatments. Results: 91 Europeangeneral practice patients (age 45.7 _+ 17.1 years) suffering from Hp-positive ulcer disease or relapsing erosive gastritis entered the study. Hp-x data per protocol (PP) and per intention to treat (IT]) are listed in the table. Conclusion: In regard to feasibility, high Hp-eradicationrates and low side effects the 7 days combination therapy of lansoprazole + clarithromycin UD + tinidazole (LCT-7d) yielded best results. Although only as few as three tablets had to be taken once daily after breakfast, Hp-eradicationrates of this new regimen resembeledthose of conventional twicea-day Hp-tberapies. Additionally, as all ulcers healed after successful Hp-eradication even using the once-a-dayapproach,there is no needto prolong lansoprazolemono-therapybeyond the 7 days of this triple treatment.
Week0 Withdrawn 8w eradn METsusc. METresist. Recrudesc, ly eradn.
RMCn(%)
RMTn(%)
RMAn(%)
OAMn(%)
Total
84 0 67/84(80) 65/80(81) 2/4 (50) 12/67(18) 55•84 (65)
80 1 48180(60) 38158(66) 10/22(45) 6/48(13) 42•80 (53)
80 0 55/80(69) 48/87 (72) 7/13 (54) 11155(20) 44180(55)
83 3 61/83(73) 50164(78) 11/19(58) 12/61 (20) 49/63(59)
327 4 231 41 190
2976 The Effect of Helicobacter pylori Eradication on Duodenal Ulcer of Scarring Stage Without Any History of Active Duodenal Ulcer Hyun Cbee Jung, Jog Sung Kim, Sang Gyun Kim, II Ju Chef, Min Jung Park, In Sung Song, Seoul National Univ Coil of Medicine, Seoul South Korea Background:Eradicationof He/icobacfer py/ori, the mainstay in curing H. py/ori-positive active duodenal ulcer, has become the standard treatment for duodenal ulcer disease. Most data support the fact that H. pylorieradication preventsduodenal ulcer relapsesand complications. However, a retevantevidence of antibacterial treatment for H. py/ori-positive duodenal ulcer
A-585
regimen
LCD
n PP (ITT)
10 O % (0 %)
LCA 19 41% (37 %)
LCT-Gd
LCT-7d
24 87 % (83 %)
38 92 % (87 %)
2974 High Efficacy of Ranitidine Bismuth Citrate, Amoxicillin, Clarithramycin and Metronidazole Twice Daily for Only Five Days in Helicobacter pylori Eradication J P. Gisbert, La Princess Univ Hosp, Madrid Spain; S Marcus, J L Gisbert, J Canter(}, J M Pajares AIM: The combination of a proton pump inhibitor (PPI) or ranitidine-bismuth citrate (Rbc) and two antibiotics during 7 to 10 days are, at present, the treatments of choice in H. pylori eradication. However, therapies for less than 7 days have been scarcely evaluatedand it is unknown whether the length of treatment can be shortened,without a lost of efficacy, if three instead of two antibiotics are used. The aim of our study was to evaluatethe efficacy of Rbc plus three antibiotics for only five days in H. pylori eradication. METHODS:We prospectively studied 100 patients (35% duodenal ulcer, 65% functional dyspepsia) infected by H. pylori. At endoscopy,biopsies were obtained for histological study and rapid ureasetest, and a ~aCurea breath test was carded out. Urea breath test was repeatedfour weeks after completing eradication treatment with Rbc (400 mg b.i.d.), amoxicillin (1 g h.i.d.), clarithromycin (500 mg b.i.d.), and metronidazole (500 mg b.i.d.). All drugs were administered together after breakfast and dinner and for five days only, and no treatment was administered thereaffer. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. RESULTS: In 98 out of the 100 patients, H. pylori eradication success or failure was assessedafter therapy (two patients were lost from follow-up). All but two of these 98 patients took all the medications (two patients stopped treatment on the third day due to nausea/vomiting). Per protocol eradication was achievedin 88•96 (92%; 95% CI, 84-96%) and in 88/100 (88%; 82-94%) by intention-to-treat. Therapy was more effective in patients with duodenal ulcer than in those with functional dyspepsia [100% vs. 82% by intention-to-treat; p
2972 Effect of Helicohacter pylori Eradication on Recurrence of Bleeding Duodenal Ulcer and Dyspeptic Symptoms:A Two-Year Prospective Study Silvano Loperfido, Rita Priora, Fabio Monica, Helena Heras Salvat, GastroenterologyUnit, Hosp ULSS 9, Treviso Italy; Luigi Angelillis, Luisa Maifreni, EmergencyMedicine Dept, Hosp ULSS 9, Treviso Italy Background Helicobacterpylorieradication reducesthe recurrencesof peptic ulcer and seems to preventrebleeding.Little is known regardingdyspepticand reflux symptoms after eradication in patients with complicated ulcer. Aims To determine the recurrence rate of ulcer and rebleeding after eradication in patients who had bled from a duodenal ulcer. To evaluate dyspeptic and reflux symptoms on long-term follow up. Methods From January 1996 to September 1998 50 consecutive H.pylori positive patients admitted for bleeding duodenal ulcer and undergoing conservative treatment were treated, as soon as oral route was reestablished, with a dual eradication regimen: ranitidine bismuth citrate 400 rng b.i.d, for four weeks, plus cladthromycin 500 mg b.i.d, for the first two weeks. Male/Femaleratio was 5.2, mean age 54 years, 25 had a history of peptic ulcer, and 10 had experiencedprevious digestive hemorrhage. Healing of the ulcer and H.pylori status were evaluated endoscopically eight weeks after initiation of therapy. Healedand eradicated patients entered a clinical and endoscopic follow up study with exclusion of NSAIDs,anti-pleteletand antisecretorydrugs. Results Forty six patients followed the protocol and were fully compliant. Eradication was achieved in 39 (78% on intention to treat analysis,85% per protocol). Thirty eight healedand eradicated patients entered the follow up study. After two years, H.pylori infection had recurred in one patient and duodenal ulcer in one H.pylori negative asymptomatic subject (2.6%). None experiencedrebleeding.Beforetreatment 12 of 38 patients complained of epigastdc pain and 7 of reflux symptoms, white B had both symptoms, After two years, four patients (liP/o) complained of mild epigastric pain, two of whom endoscopicallyshowed antral or duodenal erosions; nine patients (24%) complained of reflux symtoms, two of whom had endoscopic evidenceof esophagitis.Two other patientswith mild esophagitiswere asymptomatic.Conclusions 1) Successful H.pylori eradication prevented rehleeding from duodenal ulcer in 38 patients on follow up; 2) The two-year recurrence rate of non complicated ulcer and the reinfection rate were both 2.6%; 3) Dyspeptic symptoms, most of reflux-like type, with rare evidence of gastroduodenalerosions or esophagitis, persisted, recurred or appearedex novo in a third of patients; 4) In three asymptomatic subjects, endoscopy disclosed peptic ulcer in one and esophagitis in the other two.
2975 Curing Ulcer, Relieving Symptoms? K D. Bardhan, Pierre J. Willemse, Darren Morton, Chdstine Royston, Pamela Morris, Mary Thompson, Anne Rowland, Caroline Shaw, Hilary Allen, District Gen Hosp, Rutherham United Kingdom; Peter Roberts, Alex Godwood, Glaxo-WellcomeResearch & Development, Uxbridge United Kingdom Introduction & Aim We compared omeprazole-basedand ranitidine bismuth citrate(RBC)based H.pylori triple therapy, of which relatively little is known, assessed long-term (ly) outcome and the impact of eradication on subsequent symptoms. Method Patients with endoscopy-provenhealedDU or GU and positive rapid ureasebreathtest (UBT) were randomly allocated to receive one week twice daily RBC 400mg + metronidazole(MET) 4OOmgwith either clarithromycin 500rag (RMG), tetracycline 4OOmg(RMT) or amoxycillin lg (RMA), or omeprazole 20mg + amoxycillin lg + MET 4OOmg (DAM). Antibiotic susceptibility was assessed by disc diffusion. Eradication = negativeUBT at 8 weeks. Results (seeTable) Mean dyspepsia scores: baseline 6.4, eradication (8w,12m) 2.1, 1.9; failed eradication, 2.4, 1.6. During ly follow up after eradication (n=190), 34% required t-12RAor PPI (2_/3for preexisting reflux). Endoscopyat ly in 109/129 followed off treatment showed lesions in 30% (15 with newly developed esopbegitis, only 1 with DU) but with little or no symptoms. Discussion 1. RMGgavebetter results both at 8w & ly hut differences narrowedby ly and were about l/5th lower. 2. Eradicationrates were lower than in our previousstudies, unexplainedby antibiotic resistance alone. 3. UBT at ty may prove a better marker of treatment efficacy. 4. Symptom scores diminished at 8w, remainedlow and were similar with or without eradication. 5. Pre-existingreflux was the main reasonfor restarting H2RNPPI. 6. Peptic ulcer was cured but new esophagitis, mainly silent, developedin 14%. Conclusion RMC & DAM are similarly effective but eradication rates are much less at ly than at 8w. Reductionof symptoms seems independent of eradication. This work was supported by GlaxoWellcome.
2973 The Feasibility Of Once - Daily - Dosing H.Pylori Eradication Therapy Rodolfo E A Seelis, Gastroenterology,Aachen Germany; Werner Dohmen, Gen Medicine, Aachen Germany Background:Attempting to improve patientscompliancewe recentlyhavetried to pay attention to more innovative H.pylori (Hp) therapies. Our objective of this study was to investigate a new once-daily-dosing (qd) approach for Hp-eradication, Method: Open label, prospective, community based investigation of 4 different Hp-tdple-tberapies.A fixed combination of 30 mg lansoprazole(L) qd together with 500rag of the new sustained releaseformula of clarithromycin UD (C) qd was combined with one of the following antibiotics: 0.2 g doxycyclin (D) qd for 7 days (LOB-regimen); 2,0 g amoxycillin (A) qd for 7 days (LCA); 2.0 g tinidazole (T) qd for 6 days (LCT-6d); 1.0 g tinidazole (T) qd for 7 days (LCT-7d). Additionally, every patient once received one pretherapeutic dose of 30 mg lansoprazotethe evening before starting treatment. Hp-therapies yielding low eradication rates (Hp-x), as assessed by urease-test, histology and Hp-cuiture were discontinued quickly, those yielding Hp-x > 90 % had to be proven by at least n > 30 treatments. Results: 91 Europeangeneral practice patients (age 45.7 _+ 17.1 years) suffering from Hp-positive ulcer disease or relapsing erosive gastritis entered the study. Hp-x data per protocol (PP) and per intention to treat (IT]) are listed in the table. Conclusion: In regard to feasibility, high Hp-eradicationrates and low side effects the 7 days combination therapy of lansoprazole + clarithromycin UD + tinidazole (LCT-7d) yielded best results. Although only as few as three tablets had to be taken once daily after breakfast, Hp-eradicationrates of this new regimen resembeledthose of conventional twicea-day Hp-tberapies. Additionally, as all ulcers healed after successful Hp-eradication even using the once-a-dayapproach,there is no needto prolong lansoprazolemono-therapybeyond the 7 days of this triple treatment.
Week0 Withdrawn 8w eradn METsusc. METresist. Recrudesc, ly eradn.
RMCn(%)
RMTn(%)
RMAn(%)
OAMn(%)
Total
84 0 67/84(80) 65/80(81) 2/4 (50) 12/67(18) 55•84 (65)
80 1 48180(60) 38158(66) 10/22(45) 6/48(13) 42•80 (53)
80 0 55/80(69) 48/87 (72) 7/13 (54) 11155(20) 44180(55)
83 3 61/83(73) 50164(78) 11/19(58) 12/61 (20) 49/63(59)
327 4 231 41 190
2976 The Effect of Helicobacter pylori Eradication on Duodenal Ulcer of Scarring Stage Without Any History of Active Duodenal Ulcer Hyun Cbee Jung, Jog Sung Kim, Sang Gyun Kim, II Ju Chef, Min Jung Park, In Sung Song, Seoul National Univ Coil of Medicine, Seoul South Korea Background:Eradicationof He/icobacfer py/ori, the mainstay in curing H. py/ori-positive active duodenal ulcer, has become the standard treatment for duodenal ulcer disease. Most data support the fact that H. pylorieradication preventsduodenal ulcer relapsesand complications. However, a retevantevidence of antibacterial treatment for H. py/ori-positive duodenal ulcer
A-585