Rotapharm.az

A Comparison of 10 and 14 Days
of Lansoprazole Triple Therapy
for Eradication of Helicobacter pylori
M. Brian Fennerty, MD; T. O. G. Kovacs, MD; R. Krause, MD; M. Haber, MD;A. Weissfeld, MD; N. Siepman, MD; P. Rose, MD Background: Data from large, multicenter, US studies
in 84% (103/123) of those receiving 10-day triple therapy determining the efficacy of triple therapy for the eradi- by per-protocol analysis (95% confidence interval for treat- cation of Helicobacter pylori are lacking, especially for a ment group differences, − 10.5 to 8.1; PϾ.05). There was treatment duration of less than 14 days.
also no significant difference between the 14- and 10-day treatment groups when analyzed by an intent-to- Methods: Patients with H pylori infection and active duo-
treat analysis of H pylori eradication. A similar propor- denal ulcer disease or a history of duodenal ulcer dis- tion of patients in each treatment group reported an ease within the past year were randomized to receive 30 adverse event related to therapy (34% [46/136] vs 38% mg of lansoprazole, 1 g of amoxicillin, and 500 mg of cla- rithromycin twice daily for 10 or 14 days. The primaryefficacy end point was the eradication of H pylori as con- Conclusions: In patients with an active or a recent his-
firmed by negative histological and culture results at 4 tory of duodenal ulcer, lansoprazole-based triple therapy to 6 weeks after the completion of treatment.
for 10 or 14 days is highly effective in the eradication ofH pylori. The duration of therapy may be reduced from Results: Of 284 patients enrolled in the study from 46
14 to 10 days without a significant effect on regimen ef- US sites, 236 met the entry criteria. At 4 to 6 weeks after the end of therapy, H pylori was eradicated in 85% (96/113) of the patients receiving 14-day triple therapy and Arch Intern Med. 1998;158:1651-1656 CUREOFHelicobacterpylori method(eg,13Cureabreathtest),lackofan
intent-to-treat analysis, and lack of a com- parison of identical regimens for 14 days and less. In a single-center study, H pylori eradi- the natural history of ulcer disease.1-7 In this rectly with duration of twice-a-day triple context, numerous H pylori treatment regi- therapy (86% and 0%, respectively, with 7 mens, including an antisecretory agent with days of therapy; 90% and 6% with 10 days; 1 or 2 antibiotics, administered for 7 to 14 days have been evaluated.8-25 Since consis- the study did not detect significant differ- tently higher H pylori cure rates have been ences in efficacy between treatment groups, possibly owing to the small size of the in- based triple therapy, growing consensus fa- vors this therapy over proton pump inhibi- multicenter studies conducted in the United (Dr Kovacs); AlleghenyUniversity of the Health Recent investigation of triple anti–H py- those of shorter periods (7 to 10 days) are lori therapies has evaluated the effect of still needed to identify the ideal duration for thereby possibly increasing compliance, de- creasing adverse effects, and lowering the timal duration of triple therapy in a large, cost of treatment. Promising results (H py- lori eradication rates Ͼ90%) have been re- of patients with duodenal ulcer residing in ported in European studies of triple therapy the United States by comparing the efficacy administered for 1 week,11-21,23-25 although of a 10- and a 14-day triple therapy regimen members of the LansoprazoleStudy Group, see the the designs of most of these studies had limi- of lansoprazole, amoxicillin, and clarithro- tations, such as only 1 H pylori detection mycin to eradicate H pylori infection.
ARCH INTERN MED/ VOL 158, AUG 10/24, 1998 1998 American Medical Association. All rights reserved.
PATIENTS AND METHODS
enrollment until completion of the study (final endos-copy, 4 to 6 weeks after treatment).
Compliance, symptoms, and adverse events were as- Patients who met the entry criteria, including being 18 years sessed by returned pill count and direct questioning at each of age or older, having an active duodenal ulcer (primary treatment visit. Patients completed diaries on a daily basis lesion of Ն3 mm in diameter with visible depth) docu- during the acute phase of the study (through the week 6 mented by endoscopy or a history of endoscopically docu- visit), recording study drug dosing information, fre- mented duodenal ulcer disease within the past year, and quency of antacid consumption, and episodes of daytime being positive for H pylori as documented by positive re- and nighttime abdominal pain (defined as none, mild, mod- sults on a rapid urease test (CLOtest, Delta West Ltd, Perth, erate, or severe). Endoscopy with biopsy was repeated at Western Australia) or histological detection in gastric bi- least 4 weeks after treatment was completed (week 6 visit).
opsy specimens, were randomized to treatment. Patients The study protocol was approved by the local Insti- were subsequently dropped from the study if the presence tutional Review Board of each of the 46 participating cen- of H pylori determined by rapid urease test was not con- ters; all patients gave written informed consent.
firmed by histological findings and/or culture of biopsy speci-mens. Patients with coexisting gastric ulcer or erosive DETERMINATION OF H PYLORI STATUS
esophagitis, a history of gastroduodenal surgery, or othercomplications at the time of endoscopy were excluded, as Five biopsy specimens, 3 from the antrum and 2 from the were those using any antimicrobial agents within 2 weeks greater curvature of the corpus (3 for histological exami- prior to initiating study treatment (or within 6 weeks if such nation and 2 for culture), were obtained at each endos- use was for H pylori eradication) and those taking antiul- copy, which was performed at the screening and week 6 cer drugs in dosages indicated for ulcer disease for more visits. At the screening visit only, an additional antral bi- than 5 days within 2 weeks prior to study entry. Patients opsy specimen was obtained for the rapid urease test , and requiring anticoagulants or anti-inflammatory drugs were a serum sample was collected for determining the pres- ence of IgG antibodies to H pylori (FlexSure HP test, Smith-Kline Diagnostics Inc, San Jose, Calif).
STUDY DESIGN
Formalin-fixed, paraffin-embedded tissue sections were stained separately with hematoxylin-eosin for the evalua- Patients were stratified according to their baseline duode- tion of gastritis and Warthin-Starry stain to detect H py- nal ulcer status (active or historical) and were randomly lori. All histological preparations were evaluated by a pa- assigned within each stratum to the 14- or 10-day treat- thologist under the direction of one of us (M.H.). The ment group. All study medication was matched with pla- examining pathologist was blinded to the patients’ clini- cebo to maintain the double-blind nature of the study. Pa- cal status and treatment and to the results of other tests.
tients self-administered 5 capsules (1 of lansoprazole [30 Biopsy specimens were examined to assess the degree of mg] or placebo and 4 of amoxicillin [250 mg] or placebo) gastritis, including acute and chronic inflammation, atro- and 1 tablet of study medication (clarithromycin [500 mg] phy, and intestinal metaplasia, and graded semiquantita- or placebo) 2 times daily before breakfast and dinner for tively according to the Sydney system.28 The density of the 14 days. Patients also received antacid tablets (Gelusil, Parke- H pylori organisms was graded semiquantitatively using the Davis, Morris Plains, NJ; 0.4 g of magnesium and alumi- following scale: grade 0, negative (no organisms seen); grade num hydroxides and 25 mg of simethicone) and were 1, mild (1 to a few organisms present in a single foveola in instructed to use them only as needed for symptom at least 1 biopsy sample, but in no more than in 1 foveola); relief. Patients were instructed to avoid antiulcer and ul- grade 2, moderate (multiple clusters of organisms in 1 fo- cerogenic medication (except as noted above) and any veola or organisms in more than 1 foveola, but in less than antibiotic other than study drug or antacid from study half of the foveola); and, grade 3, severe (numerous received previous therapy for gastrointestinal disorders(89% and 79% of patients in the 10- and 14-day treat- Two hundred eighty-four patients were enrolled in the ment groups, respectively; PϽ.05). The presence of an study based on positive rapid urease test results and were endoscopically documented ulcer or a history of ulcer randomized to receive lansoprazole, amoxicillin, and cla- was established, and the presence of H pylori was con- rithromycin twice daily for 10 (n = 148) or 14 days firmed by histologic examination and/or culture of bi- (n = 136). The treatment groups were well matched at opsy specimens in 258 of the 284 patients. Because of baseline in relation to most demographic characteris- various protocol violations (eg, no H pylori assessment tics, duodenal ulcer status, and histological gastritis at the week 6 visit, noncompliance, or other antibiotic (Table 1). There was a significant difference between
usage), 236 of the 258 patients were included in the per- the treatment groups with respect to race: 61% of the pa- protocol analysis of H pylori eradication.
tients in the 10-day treatment group were white, com-pared with 51% of the 14-day treatment group. Most pa- ERADICATION OF H PYLORI
tients (86% and 89% of patients in the respective treatmentgroups) had an endoscopically documented duodenal ul- Helicobacter pylori was eradicated from 103 (84%) of 123 cer at baseline, and the majority of enrolled patients had patients in the 10-day treatment group and from 96 (85%) ARCH INTERN MED/ VOL 158, AUG 10/24, 1998 1998 American Medical Association. All rights reserved.
organisms diffusely present in half or more foveolae in a exceed 15%, assuming the true eradication rate of the bet- ter of the 2 treatment groups was 85% and that the dif- Biopsy specimens for culture were transported in modi- ference between the true eradication rates was no greater fied Stuart transport media, inoculated to both selective and nonselective media, and incubated at 37°C in microaero- A per-protocol analysis and a more conservative (worst bic conditions. The H pylori organisms were morphologi- case), intent-to-treat analysis, which included patients with cally identified by Gram stain and the production of cata- missing data as failures, were conducted for H pylori eradi- lase, oxidase, and urease. Clarithromycin and amoxicillin cation. Patients who prematurely discontinued taking study (using ampicillin) susceptibility testing was performed us- medication owing to a treatment-related adverse event, who ing the epsilometer test (E-test, AB Biodisk, Solna, Swe- were considered a therapeutic failure, or who required an den). Minimal inhibitory concentrations (MICs) of Յ0.5 antiulcer or antireflux drug were included in the per- µg/mL and Ͼ2 µg/mL indicated susceptibility and resis- protocol analysis of H pylori eradication, and patients who tance, respectively, to clarithromycin. An ampicillin MIC prematurely discontinued treatment because of 1 of these of Յ0.25 µg/mL indicated susceptibility to amoxicillin; there reasons and were missing the posttreatment H pylori eradi- are currently no known H pylori isolates resistant to amoxi- cation assessment were included in the analysis as treat- cillin. Microbiological testing was conducted at a central ment failures (6 patients in this study). An intent-to-treat laboratory (Microbiology Specialists Inc, Houston, Tex) un- analysis was performed for gastritis and patient diary data.
der the direction of 1 of us (A.W.).
The comparability of the treatment groups was as- At screening, the presence of H pylori was defined by sessed with respect to demographic variables and medical at least 2 positive test results (rapid urease test and either and social histories by the ␹2 test and 1-way analysis of vari- histological examination and/or culture). A total of 22 pa- ance. Baseline gastritis findings were compared among the tients were excluded from the efficacy analysis owing to a treatment groups using Cochran-Mantel-Haenszel meth- lack of H pylori organisms at baseline: 20 patients had H odology for ordered response variables.
pylori documented by only 1 test; and H pylori was not docu- Differences between the treatment groups at the week mented by any test for the remaining 2 patients. Eradica- 6 visit with respect to H pylori eradication were assessed us- tion was defined as both histological studies and cultures ing the Cochran-Mantel-Haenszel test, with baseline duo- being negative for H pylori organisms at least 4 weeks af- denal ulcer status (active or healed) and investigator’s geo- graphic region as stratification factors. Exact binomial 95%confidence intervals for H pylori eradication were con- STATISTICAL ANALYSIS
structed for each treatment group and for the difference inH pylori eradication rates between the treatment groups. The Equivalence of the 2 treatment groups was evaluated ac- treatment groups were also compared after adjusting for con- cording to criteria developed by the Anti-Infective Divi- comitant factors using the Cochran-Mantel-Haenszel test.
sion of the Food and Drug Administration. These criteria Resolution or improvement of gastritis from baseline required that the absolute value of the lower bound of the to the week 6 visit was assessed using the Cochran-Mantel- 95% confidence interval for the difference between treat- Haenszel test. The mean severity of daytime and night- ments not exceed 15% if the eradication rate for the better time abdominal pain, the percentage of days and nights with of the 2 treatment groups was between 80% and 89%.
abdominal pain, the mean number of antacid tablets taken A sample size of at least 260 (130 patients in each treat- per day, and the percentage of days that antacid was used ment group) was chosen to achieve at least an 80% chance during the treatment and posttreatment periods were com- that the absolute value of the lower bound of the 95% con- pared between treatment groups using the Wilcoxon 2- fidence interval for the difference between the 2 treatment sample test. The Fisher exact test was used to compare the groups in H pylori eradication rates at the week 6 visit (4 incidence of treatment-related adverse events (defined as to 6 weeks after the completion of treatment) did not possibly or probably related) between the treatment groups.
of 113 in the 14-day treatment group. The 95% confi- rates between the 2 treatment groups ( − 9.7 to 9.1) also dence interval for the difference in H pylori eradication supporting the conclusion of equivalence.
rates between the treatment groups ( − 0.5 to 8.1) sup-ported the conclusion of equivalence of the 2 treatment ULCER STATUS
groups based on the predefined criteria (Table 2). This
observation was unaffected after adjustment for poten-
Among the evaluable patients enrolled with an active ul- tially influential factors, including investigator, sex, race, cer (n = 228), 166 did not have an ulcer at the final en- age, study drug compliance, baseline H pylori grade, base- doscopy, which was conducted 4 weeks after the comple- line duodenal ulcer status (active or historical), base- tion of therapy. There was no statistically significant line size of the index ulcer, and alcohol, tobacco, or caf- difference in ulcer status between the 10- and 14-day treat- feine use. By a worst-case intent-to-treat analysis, in which patients who failed to return for the follow-up evalua-tion were considered to have persistent H pylori infec- RESOLUTION OF GASTRITIS
tion, the H pylori eradication rates were 81% (110/135)and 82% (103/126), respectively, with the 95% confi- Patients experienced improvement or resolution of his- dence interval for the difference in H pylori eradication tological markers of chronic gastritis at the week 6 fol- ARCH INTERN MED/ VOL 158, AUG 10/24, 1998 1998 American Medical Association. All rights reserved.
Table 1. Pretreatment Characteristics of Patients
Table 2. Helicobacter pylori Eradication at 4 to 6 Weeks
With Active or Recent History of Duodenal Ulcer
Posttreatment by Lansoprazole, Amoxicillin,
Randomized to Receive Lansoprazole, Amoxicillin,
and Clarithromycin Treatment Group*
and Clarithromycin for 10 or 14 Days*
Characteristic
†95% CI for difference refers to H pylori eradication rates between tients with primary clarithromycin resistance, H pylori was eradicated from 1 of 6 patients in the 10-day therapy group and from 7 of 11 patients in the 14-day therapy Development of antibiotic resistance during treat- ment with lansoprazole-based triple therapy was an *All values other than age are expressed as number (percentage).
infrequent occurrence. Of the 107 patients who had iso- lates susceptible to clarithromycin pretreatment, 2 were ‡Smoker defined as any usage of tobacco.
§Alcohol use defined as consumption of any quantity of alcohol on a positive for H pylori and had susceptibility results at the week 6 visit. Neither of these patients had a persistentinfection caused by clarithromycin-resistant organisms.
low-up visit compared with the pretreatment visit. In an Three patients in the 10-day treatment group and 1 intent-to-treat analysis, no statistically significant differ- patient in the 14-day treatment group who had no cla- ences were observed between the 10- and 14-day treat- rithromycin susceptibility results before treatment had ment groups in the percentage of patients showing reso- an isolate resistant to clarithromycin after treatment.
lution or improvement of acute inflammation (91% each None of the patients with an amoxicillin-susceptible H [115/127] vs [107/117], respectively) and chronic in- pylori isolate developed resistance to amoxicillin after flammation (28% [36/128] and 21% [24/117], respec- tively). Among the few patients with atrophy at base-line, resolution of findings was observed for 6 of 7 patients.
RESOLUTION OF SYMPTOMS
No patient had intestinal metaplasia at baseline or at theweek 6 visit.
After controlling for H pylori eradication status, no sta-tistically significant differences were observed between ANTIMICROBIAL SUSCEPTIBILITY
the treatment groups for either the frequency or the meanseverity of daytime or nighttime abdominal pain during Helicobacter pylori was cultured before the initiation of the treatment period. Similarly, the treatment groups were treatment, and susceptibility data were available for 124 comparable based on patients’ consumption of antacid study patients. Culture and susceptibility data were not tablets during the study. However, a statistically signifi- available for 137 patients (7 who had positive culture re- cant difference was observed for the frequency and the sults but no susceptibility results and 130 patients who mean severity of daytime abdominal pain during the fol- had negative culture results). Ninety-eight percent (122/ 124) of the isolates were susceptible to amoxicillin us-ing the MIC criterion of Յ0.25 µg/mL. The MICs for the COMPLIANCE AND ADVERSE EFFECTS
2 isolates that were not within this range were 2 µg/mLand Ͼ256 µg/mL. Neither isolate was retested by the ep- At least 90% of patients in each of the treatment groups silometer test. The agar dilution result for the isolate origi- took more than 90% of their study medication. Twelve nally found to be 2 µg/mL was 0.5 µg/mL; the second iso- patients (2 and 10 in the 10- and 14-day treatment groups, late was not available for agar dilution MIC testing. Thus, respectively) took less than 70% of study medication; none the purported resistance to amoxicillin could not be con- and 7 of these patients in the respective treatment groups firmed. Eighty-six percent (107/124) of the isolates were were excluded from the per-protocol analysis for H py- lori eradication, and the remaining 5 patients were clas- Among the 107 patients infected with clarithromy- sified as failures. Nine patients discontinued taking the cin-susceptible isolates, H pylori was eradicated from 93% study medication prematurely at least in part because of (53/57) and 96% (48/50) of the patients in the 10- and drug-related adverse events (3 and 6 patients in the re- 14-day treatment groups, respectively. Among the 17 pa- ARCH INTERN MED/ VOL 158, AUG 10/24, 1998 1998 American Medical Association. All rights reserved.
The 2 treatment regimens were comparable based The H pylori eradication rates using the intent-to- on the percentage of patients who reported a treatment- treat analysis in this study are similar to those that have related adverse event: 38% (56/148) of the patients in the been reported with other proton pump inhibitor–based 10-day treatment group and 34% (46/136) of the pa- triple therapy, while per-protocol analysis rates are nu- tients in the 14-day treatment group. The most com- merically lower.11-25 This difference between per- monly reported events were diarrhea and taste distur- protocol efficacy is because patients who prematurely dis- bance, with no statistically significant differences between continued taking the study medication because of a treatment groups for any specific drug-related adverse treatment-related adverse event or who required an an- event. The majority of treatment-related adverse events tiulcer or antireflux medication were included as thera- experienced by study patients were mild or moderate in peutic failures in the per-protocol analysis of our study.
These types of patients have generally been excluded fromefficacy evaluations in other studies of anti–H pylori treat- ment regimens, resulting in more favorable results. Weincluded these patients in our analyses to more realisti- While the medical literature over the last decade is re- cally simulate the efficacy of H pylori treatment that can plete with H pylori treatment studies, the optimal dura- tion of triple therapy, especially for US patients, has not The 14% prevalence of primary clarithromycin re- been adequately evaluated, and consensus is lacking. Most sistance found in our study is higher than the 5% to 8% comparisons have been based on results from separate, prevalence previously reported from studies conducted European trials that have used different methods, failed in the United States.31,32 As expected based on the re- to use multiple diagnostic tests to document the pres- sults of others,33 we found the H pylori eradication rate ence of H pylori and verify eradication, and failed to of a clarithromycin-containing triple therapy regimen is include intent-to-treat analyses or enroll sufficient num- compromised in patients infected with a clarithromycin- bers to detect significant differences. This trial incorpo- resistant organism: H pylori eradication in 94% of pa- rated these important features to compare in a US study tients infected with clarithromycin-susceptible strains and the efficacy and tolerability of lansoprazole-based triple 47% of patients with clarithromycin-resistant strains. Our results are also consistent with those of Wurzer et al34 Earlier research has demonstrated 14-day triple and Schwartz et al,29 who suggested that secondary cla- therapy with lansoprazole, clarithromycin, and amoxi- rithromycin resistance develops infrequently among pa- cillin to be effective in eradicating H pylori in up to 94% tients treated with a proton pump inhibitor combined with of patients.29 When a rigorous Food and Drug Adminis- clarithromycin and another antibiotic.
tration–directed analysis was used (that included pa- The results of our study as well as those from the tients as treatment failures who dropped out of the study study by Laine et al27 suggest that twice-a-day triple after experiencing adverse events considered possibly or therapy for 10 days leads to high rates of H pylori eradi- probably treatment related), the H pylori eradication rate cation, tolerability, and compliance. Thus, while 14-day with 14-day lansoprazole-based triple therapy was 92%.30 therapy with lansoprazole, amoxicillin, and clarithro- The results of this study are similar for both a 10- and a mycin has recently received approval from the Food and 14-day regimen. The treatment groups were found to be Drug Administration, these and other results from on- comparable based on cure of H pylori infection, resolu- going research may eventually lead to a shorter, 10-day tion or improvement of gastritis markers, frequency and mean severity of daytime or nighttime abdominal pain,patients’ antacid use, and tolerability. Equivalent H py- lori eradication rates were achieved when standard, 14-day triple therapy with lansoprazole, amoxicillin, and cla- In patients with an active or a recent history of duode- rithromycin twice daily was shortened to 10 days (85% nal ulcer, lansoprazole-based triple therapy for 10 or 14 and 84%, respectively) (Table 2). The eradication rates days is highly effective in the eradication of H pylori in- for the respective treatment groups in the worst-case in- fection. The duration of therapy may be reduced from tent-to-treat analysis (82% and 81%) were similar to those 14 days to 10 days without a significant effect on the regi- from the per-protocol analysis, illustrating the robust- ness of lansoprazole-based triple therapy and the impor-tance of including both analyses in order to compare re- Accepted for publication January 8, 1998. sults from different trials. Inclusion of patients without This study was supported in part by a grant from TAP H pylori eradication data and classifying them as treat- ment failures in the intent-to-treat analysis resulted in The members of the Lansoprazole Study Group are as high H pylori eradication rates that still compare favor- follows: M. Radwan Al-Sabbagh, Houston, Tex; Dennis Avner, ably with the outcomes of dual therapy when it was stud- Salt Lake City, Utah; Simmy Bank, New Hyde Park, NY; ied under the least stringent study methodologies (eg, Thomas Bianchi, Tallassee, Ala; Gregory V. Collins, Char- per-protocol analysis that excluded patients with miss- lotte, NC; Alan Cutler, Detroit, Mich; Monte G. Finch, Mur- ing data, patients who prematurely discontinued taking ray, Ky; Stephen Freeman, Denver, Colo; Walter Gaman, study medication or did not return for a posttreatment Irving, Tex; Charles A. Gluck, Pembroke Pines, Fla; Ver- visit, and patients with an unhealed ulcer following the non G. K. Hee, Vancouver, Wash; Jon Isenberg, San Diego, Calif; Neil Kassman, Statesville, NC; Mukui Khandelwal, ARCH INTERN MED/ VOL 158, AUG 10/24, 1998 1998 American Medical Association. All rights reserved.
Hershey, Pa; Jong Koo Kim, Chicago, Ill; Phillip K. 13. Buckley M, Xia HX, Hyde D, et al. A cost-effective European approach to H pylori Kiyasu, Portland, Ore; Mark Lamet, Hollywood, Fla; eradication [abstract]. Gut. 1995;37(suppl 1):A91. Abstract 363.
14. Bazzoli F, Zagari RM, Fossi S, et al. Efficacy and tolerability of a short-term, low- Michael Levine, Marietta, Ga; Ralph T. Lyerly, Birmingham, dose triple therapy for eradication of Helicobacter pylori [abstract]. Am J Gas- Ala; Gustavo Machicado, Van Nuys, Calif; Paul N. Maton, troenterol. 1994;89(suppl):1364. Abstract 317.
Oklahoma City, Okla; Mark J. Provenza, Shreveport, La; 15. Bazzoli F, Guillini S, Zagari RM, et al. Effect of omeprazole and clarithromycin Ronald Pruitt, Nashville, Tenn; A. B. Reddy, Tuscaloosa, plus tinidazole on the eradication of Helicobacter pylori and the recurrence of Ala; Dennis E. Riff, Anaheim, Calif; Lee Rocamora, Winston- duodenal ulcer [abstract]. Gut. 1995;37(suppl 1):A5. Abstract 18.
16. Dalia Libera M, Pazzi P, Carli G, et al. High effectiveness and safety of one-week Salem, NC; Kathryn Ross, Newport Beach, Calif; Herbert antibiotic regimen in Helicobacter pylori eradication. Aliment Pharmacol Ther.
Rubin, Beverly Hills, Calif; Gary Ruoff, Kalamazoo, Mich; Michael Safdi, Cincinnati, Ohio; Bruce Sahba, San Diego; 17. Jaup BH, Norrby A. Comparison of two low-dose one-week triple therapy regi- Howard Schwartz, Juniper, Fla; Michael Schwartz, West mens with and without metronidazole for cure of H. pylori infection [abstract].
Gut. 1995;37(suppl 1):A43. Abstract 170.
Palm Beach, Fla; Umed Shah, Leonardtown, Md; Douglas 18. Jaup BH, Norrby A. Low-dose short-term triple therapy for cure of Helicobacter Simon, Bronx, NY; William Snape, Long Beach, Calif; Roger pylori infection and healing of peptic ulcers. Am J Gastroenterol. 1995;90:943- Soloway, Galveston, Tex; Lewis Strong, Loveland, Colo; James D. Torosis, Redwood City, Calif; Gopikrishnan 19. Xia HX, Buckley M, Hyde D, et al. Effects of antibiotic-resistance in clarithromycin- Vasudevan, Detroit; Peter Witt, Greeley, Colo; Robert combined triple therapy for Helicobacter pylori [abstract]. Gut. 1995;37(suppl1):A55. Abstract 218.
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ARCH INTERN MED/ VOL 158, AUG 10/24, 1998 1998 American Medical Association. All rights reserved.

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