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Eradication of Helicobacter pylori or H2 blocker maintenance therapy after peptic ulcer bleeding- A prospective randomized trial
A156
AGA ABSTRACTS
Q THE RISK OF SERIOUS UPPER GI COMPLICATIONS IS CONSTANT WITH CONTINUOUS NSAID THERAPY: RESULTS OF A RECORD LINKAGE STUDY IN 52,382 EXPOSED PATIENTS. TM MacDonald, *SV Morant, *GC Robinson, *MJ Shield, FE Murray, DG MeDevitt. Medicines Monitoring Unit, Dept of Clinical Pharmacology, Ninewells Hospital, University of Dundee, and *Searle, High Wycombe, UK The profile of risk during and after treatment with NSAIDs remains poorly defined. The AIM of this study was to characterise the risk profile of NSAID therapy. METHOD: We studied the cohort of patients > 50 yr who received one or more NSAID prescriptions between Jan 1st 1989 - Dec 31st 1991. Using record-linkage methodology, we prospectively constructed a population based (n=400,000) database containing (a) data on all dispensed community NSAID and ulcer healing drug prescriptions and (b) all validated upper gastrointestinal haemorrhage and perforations (GHP). NSAID exposure was defined as the 45 day period following a prescription. Risk profiles from the start of continuous NSAID exposure and non-exposure were constructed. Odds ratios (95% CI) were estimated by Poisson regression relative to event rates prior to NSAID exposure. Event rates are given per thousand patient years (TPY). RESULTS: 52,382 patients received 297,574 NSAID prescriptions totalling 29,703 patient years of NSAID exposure and 125,954 patient years of non-exposure. There were 430 GHP events (208 exposed). The event rate in patients with a history of an upper gastrointestinal event (UGIH) was high regardless of NSAID exposure (111 per TPY exposed v 90 non-exposed, OR 1.5 (0.6-3.6)), but the 0.4% of patients with a history accounted for only 7.7% of events. In patients without UGI history the GHP rate was much lower (7.0 per TPY on NSAID, 1:8 off NSAID), but with a higher and significant odds ratio, OR 7.3 (5.2-1021). This risk was constant during continuous exposure (7.0 per TPY) and remained significantly higher for 1 month following end of exposure, OR 4.8 (3.1-7.4).. GHP risk was related to dose of NSAID (low v high OR 1.5 (1.1-2.1)) and age (80-89y v 50-59y OR 6.5 (CI 3.811.0) but not with sex. The dose adjusted rank order of toxicity was azapropazone > piroxicam > flurbiprofen > ketoprofen > diclofenac SR > diclofenac > naproxen > mefenamic acid > ibuprofen > indomethacin > nabumetone > fenbufen. Summary: The risk of GHP was constant with continuous NSAID treatment. There was a carry over period of risk of at least one month after exposure had ceased. This large study confirms the rank order of NSAID toxicity reported in previous studies and also confirms increased risk with increasing age or NSAID dose. Prior UGIH is independently the most important risk factor for GHP. This research funded in part by Searle, High Wycombe, UK.
"O ERADICATION OF Heficobacterpylod OR H2 BLOCKER MAINTENANCE THERAPY AFTER PEPTIC ULCER BLEEDING- A PROSPECTIVE RANDOMIZED TRIAL. M.Maier*, D. Schilling*, D. Dorlars*, K. Wegener** B. Kohler*, C. Benz*, J.F. Riemann*. Dept. of Gastroenterology* and Dept. of Pathology**, Klinikum Ludwigsbafen, Germany H2 Blocker maintenance therapy reduced rebleeding and ulcer relaps after hemorrhage from duodenal ulcer (Gastroenterology, 1990,98, A 65) and also for eradication of Helicobacterpylori a protective effect after ulcer bleeding has been shown (Scand J Gastroentero11993,28,939-942). We initiated a prospective randomized study to compare the 2 therapys for prevention of relaps after bleeding from Helicobacter pylo# associated peptic ulcer since this has to our knowledge not been investigated until now and clinical trials are recomended (JAMA,1994,272,65-69). Ulcer bleeding was treated endoscopically and Helicobacterpylod infection proved by histology and urease test. NSAID medication was a criterion for exclusion. Eradication was induced by 60 mg omeprazole b.i.d, and amoxicilline 750 mg t.i.d, for 10 days initially and maintenance therapy consisted of 150rag ranitidine daily after ulcer healing. Therapy for primary ulcer healing was 20 to 40 mg omeprazole and 30Omg ranitidine respectively for 4 weeks. Negative histology, urease test and C13 breath test 4 weeks after the end of therapy were criter a for successfu eradicat on of
Helicobacter pylon.
89 patients (pts)were randomized since Aug. 1992, 46 for eradication (A) and 43 (B) for ranitidine. Both groups beeing comparable for age, sex, ulcer location and bleeding activity. The average clinical follow-up is 10 month.The overall eradication rate in group A was 38 / 40 pts (90%, twice after a second course of medication only). 21 pts (A) and 25 pts (B) have reached the first year follow up control. 1 pts (5%) in group A had ulcer relaps and 2 out of 21 pts were Hp positiv at I year control. 6 pts in group B had ulcer relaps (21%) with rebleeding in 3 cases. 3 of the 6 pts boeing non-compliant. CONCLUSION: preliminary data of our prospective trial prove eradication of Heficobacter pylod with omeprozole and amoxicilline effective in preventing further complication after peptic ulcer bleeding. Eradication may become the therapy of choice since ranitidine maintenance might be less effective, probably due to compliance problems.(The trial was partially supported by Astra Chemicals, Wedel, Germany)
GASTROENTEROLOGY, Vol. 108, No. 4
DIURNAL VARIATION 1N PHARMACOKINETICS AND PHARMACODYNAMICS OF NIZATIDINE IN HEALTHY VOLUNTEERS AND 1N PATIENTS WITH DOUDENAL ULCER: V. Mahachai, F. Jamali, A.B.R. Thomson, P. Kirdeikis, M. Tavernini, L. Zuk, B. Marriage, and I. Simpson: Faculty of Pharmacy and the Nutrition and Metabolism Research Group, Division of Gastroenterology, and Clinical Investigation Unit: University of Alberta, CANADA and Chulalongkorn University, THAILAND: Six healthy volunteers (HV) and six patients with asymptomatic duodenal ulcer disease (DU) received placebo, 300 nag nizatidine once at night (qhs) or twice daily (bid, morning and evening) for a week in a random, cross-over fashion. Steady-state serum nizatidine concentration and gastric pH were measured over a 24 h period. No significant differences in the pharmacokinetic indices were observed between the HV and DU groups. Significantly lower peak serum concentrations, longer t~r2 and larger volume of distributions were observed after the evening as Compared to the bid dose. The diurnal variation in drug kinetics between the nighttime and daytime bid dose may be caused by a slower absorption rate, paralleled with a higher extent of distribution. Despite the lower serum nizatidine concentrations, gastric pH was higher in the evening than in the daytime; we speculate that this was due to a timedependent enhanced distribution of the H2-receptor blocker into the site of action.
CLARITHROMYCIN VERSUS AMOXYCILLIN IN A DUAL HIGHDOSE OMEPRAZOLE-BASED REGIMEN FOR H.PYLORI ERADICATION P.Malfertheiner, J.E.Dominguez-Mufioz, J.Heller, T.Sauerbruch. Department of Internal Medicine, University of Bonn, Germany. Omeprazole does favorably combine with either amoxycillin or clarithromycin for the eradication of H.pylori. T h e amoxycillin effect is enhanced by high-dose omeprazole but this is not shown for cladthromycin. This study aimed at defining the relative role of the two antibiotics in combination with identical high-dose omeprazole. Material and Methods. 38 patients with relapsing severe dyspeptic symptoms, without evidence of active peptic ulceration were assigned to either treatment A: Omeprazole 40 mg b.i.d, and clarithromyein 500 mg b.i.d, or treatment B: Omeprazole 40 nag b.i.d, and amoxycillin 1 g b.i.d. for two weeks. Detection of H.pylori was based on direct tests (urease, histology) and 13C-UBT before treatment. Eradication was tested 4 and 8 weeks after the end of treatment by 13C-UBT. Results. In group A 18 patients completed the treatment and H.pylori eradication was achieved in 83%. In group B 17 patients completed the treatment and eradication was achieved in 71%. One patient had to discontinue the treatment because of cutaneous rash after the first week. All 6 patients with persisting H.pylori after the first treatment were rechallenged with a triple regimen consisting of omeprazole plus amoxycillin plus clarithromyein in the original dose used for the first treatment. H.pylori was eradicated in all these patients. Conclusions. Both antibiotics show a high efficacy in combination with high-dose omeprazole, but clarithromycin resulted to be superior to amoxycillin in the dual regimen. Re.challenge of nonresponders to a triple combination with the previously used antibiotics was always successful.
AGA ABSTRACTS
Q THE RISK OF SERIOUS UPPER GI COMPLICATIONS IS CONSTANT WITH CONTINUOUS NSAID THERAPY: RESULTS OF A RECORD LINKAGE STUDY IN 52,382 EXPOSED PATIENTS. TM MacDonald, *SV Morant, *GC Robinson, *MJ Shield, FE Murray, DG MeDevitt. Medicines Monitoring Unit, Dept of Clinical Pharmacology, Ninewells Hospital, University of Dundee, and *Searle, High Wycombe, UK The profile of risk during and after treatment with NSAIDs remains poorly defined. The AIM of this study was to characterise the risk profile of NSAID therapy. METHOD: We studied the cohort of patients > 50 yr who received one or more NSAID prescriptions between Jan 1st 1989 - Dec 31st 1991. Using record-linkage methodology, we prospectively constructed a population based (n=400,000) database containing (a) data on all dispensed community NSAID and ulcer healing drug prescriptions and (b) all validated upper gastrointestinal haemorrhage and perforations (GHP). NSAID exposure was defined as the 45 day period following a prescription. Risk profiles from the start of continuous NSAID exposure and non-exposure were constructed. Odds ratios (95% CI) were estimated by Poisson regression relative to event rates prior to NSAID exposure. Event rates are given per thousand patient years (TPY). RESULTS: 52,382 patients received 297,574 NSAID prescriptions totalling 29,703 patient years of NSAID exposure and 125,954 patient years of non-exposure. There were 430 GHP events (208 exposed). The event rate in patients with a history of an upper gastrointestinal event (UGIH) was high regardless of NSAID exposure (111 per TPY exposed v 90 non-exposed, OR 1.5 (0.6-3.6)), but the 0.4% of patients with a history accounted for only 7.7% of events. In patients without UGI history the GHP rate was much lower (7.0 per TPY on NSAID, 1:8 off NSAID), but with a higher and significant odds ratio, OR 7.3 (5.2-1021). This risk was constant during continuous exposure (7.0 per TPY) and remained significantly higher for 1 month following end of exposure, OR 4.8 (3.1-7.4).. GHP risk was related to dose of NSAID (low v high OR 1.5 (1.1-2.1)) and age (80-89y v 50-59y OR 6.5 (CI 3.811.0) but not with sex. The dose adjusted rank order of toxicity was azapropazone > piroxicam > flurbiprofen > ketoprofen > diclofenac SR > diclofenac > naproxen > mefenamic acid > ibuprofen > indomethacin > nabumetone > fenbufen. Summary: The risk of GHP was constant with continuous NSAID treatment. There was a carry over period of risk of at least one month after exposure had ceased. This large study confirms the rank order of NSAID toxicity reported in previous studies and also confirms increased risk with increasing age or NSAID dose. Prior UGIH is independently the most important risk factor for GHP. This research funded in part by Searle, High Wycombe, UK.
"O ERADICATION OF Heficobacterpylod OR H2 BLOCKER MAINTENANCE THERAPY AFTER PEPTIC ULCER BLEEDING- A PROSPECTIVE RANDOMIZED TRIAL. M.Maier*, D. Schilling*, D. Dorlars*, K. Wegener** B. Kohler*, C. Benz*, J.F. Riemann*. Dept. of Gastroenterology* and Dept. of Pathology**, Klinikum Ludwigsbafen, Germany H2 Blocker maintenance therapy reduced rebleeding and ulcer relaps after hemorrhage from duodenal ulcer (Gastroenterology, 1990,98, A 65) and also for eradication of Helicobacterpylori a protective effect after ulcer bleeding has been shown (Scand J Gastroentero11993,28,939-942). We initiated a prospective randomized study to compare the 2 therapys for prevention of relaps after bleeding from Helicobacter pylo# associated peptic ulcer since this has to our knowledge not been investigated until now and clinical trials are recomended (JAMA,1994,272,65-69). Ulcer bleeding was treated endoscopically and Helicobacterpylod infection proved by histology and urease test. NSAID medication was a criterion for exclusion. Eradication was induced by 60 mg omeprazole b.i.d, and amoxicilline 750 mg t.i.d, for 10 days initially and maintenance therapy consisted of 150rag ranitidine daily after ulcer healing. Therapy for primary ulcer healing was 20 to 40 mg omeprazole and 30Omg ranitidine respectively for 4 weeks. Negative histology, urease test and C13 breath test 4 weeks after the end of therapy were criter a for successfu eradicat on of
Helicobacter pylon.
89 patients (pts)were randomized since Aug. 1992, 46 for eradication (A) and 43 (B) for ranitidine. Both groups beeing comparable for age, sex, ulcer location and bleeding activity. The average clinical follow-up is 10 month.The overall eradication rate in group A was 38 / 40 pts (90%, twice after a second course of medication only). 21 pts (A) and 25 pts (B) have reached the first year follow up control. 1 pts (5%) in group A had ulcer relaps and 2 out of 21 pts were Hp positiv at I year control. 6 pts in group B had ulcer relaps (21%) with rebleeding in 3 cases. 3 of the 6 pts boeing non-compliant. CONCLUSION: preliminary data of our prospective trial prove eradication of Heficobacter pylod with omeprozole and amoxicilline effective in preventing further complication after peptic ulcer bleeding. Eradication may become the therapy of choice since ranitidine maintenance might be less effective, probably due to compliance problems.(The trial was partially supported by Astra Chemicals, Wedel, Germany)
GASTROENTEROLOGY, Vol. 108, No. 4
DIURNAL VARIATION 1N PHARMACOKINETICS AND PHARMACODYNAMICS OF NIZATIDINE IN HEALTHY VOLUNTEERS AND 1N PATIENTS WITH DOUDENAL ULCER: V. Mahachai, F. Jamali, A.B.R. Thomson, P. Kirdeikis, M. Tavernini, L. Zuk, B. Marriage, and I. Simpson: Faculty of Pharmacy and the Nutrition and Metabolism Research Group, Division of Gastroenterology, and Clinical Investigation Unit: University of Alberta, CANADA and Chulalongkorn University, THAILAND: Six healthy volunteers (HV) and six patients with asymptomatic duodenal ulcer disease (DU) received placebo, 300 nag nizatidine once at night (qhs) or twice daily (bid, morning and evening) for a week in a random, cross-over fashion. Steady-state serum nizatidine concentration and gastric pH were measured over a 24 h period. No significant differences in the pharmacokinetic indices were observed between the HV and DU groups. Significantly lower peak serum concentrations, longer t~r2 and larger volume of distributions were observed after the evening as Compared to the bid dose. The diurnal variation in drug kinetics between the nighttime and daytime bid dose may be caused by a slower absorption rate, paralleled with a higher extent of distribution. Despite the lower serum nizatidine concentrations, gastric pH was higher in the evening than in the daytime; we speculate that this was due to a timedependent enhanced distribution of the H2-receptor blocker into the site of action.
CLARITHROMYCIN VERSUS AMOXYCILLIN IN A DUAL HIGHDOSE OMEPRAZOLE-BASED REGIMEN FOR H.PYLORI ERADICATION P.Malfertheiner, J.E.Dominguez-Mufioz, J.Heller, T.Sauerbruch. Department of Internal Medicine, University of Bonn, Germany. Omeprazole does favorably combine with either amoxycillin or clarithromycin for the eradication of H.pylori. T h e amoxycillin effect is enhanced by high-dose omeprazole but this is not shown for cladthromycin. This study aimed at defining the relative role of the two antibiotics in combination with identical high-dose omeprazole. Material and Methods. 38 patients with relapsing severe dyspeptic symptoms, without evidence of active peptic ulceration were assigned to either treatment A: Omeprazole 40 mg b.i.d, and clarithromyein 500 mg b.i.d, or treatment B: Omeprazole 40 nag b.i.d, and amoxycillin 1 g b.i.d. for two weeks. Detection of H.pylori was based on direct tests (urease, histology) and 13C-UBT before treatment. Eradication was tested 4 and 8 weeks after the end of treatment by 13C-UBT. Results. In group A 18 patients completed the treatment and H.pylori eradication was achieved in 83%. In group B 17 patients completed the treatment and eradication was achieved in 71%. One patient had to discontinue the treatment because of cutaneous rash after the first week. All 6 patients with persisting H.pylori after the first treatment were rechallenged with a triple regimen consisting of omeprazole plus amoxycillin plus clarithromyein in the original dose used for the first treatment. H.pylori was eradicated in all these patients. Conclusions. Both antibiotics show a high efficacy in combination with high-dose omeprazole, but clarithromycin resulted to be superior to amoxycillin in the dual regimen. Re.challenge of nonresponders to a triple combination with the previously used antibiotics was always successful.