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The 13C-urea breath test for early assessment of Helicobacter pylori eradication
April 1 9 9 5
D O U B L E - B L I N D T R I A L OF L ~ S O P I ~ Z O L E + P~IOXICILLIN VS. L~NSOPI~ZOLE ÷ CLARITHROMYCIN FOR CURE OF
HELICOBACTER PYLORI INFECTION IN D U O D E N A L ULCER PATIENTS E. BaverdSrffer, H. Schulz, T. Simon, W. HSchter, J. Weingart, H. Porst, E. B~stlein, G.A. Mannes, A. Sommer, H.D. Bundschu, A. Meining, M. Stolte, D e p a r t m e n t of Internal M e d i c i n e II, K l i n i k u m Gro6hadern, U n i v e r s i t y of Munich, and the Ulcer Study Group, Germany. Background: Anti-Helicobacter pylori (HP) treatment u s i n g p r o t o n pump inhibitors and antibiotics is a v e r y promising option. ~im: The aim of the present study was to investigate w h e t h e r combinations of h i g h dose [ansopra2ole (LAN) and antibiotics achieve olinical~y usefull HP cure rates (> 80 %). Methods= 60 patients with an HP-associated duodenal u l c e r (DU) were randomly treated with either ~0 m g L A N bid or 90 mg LAN (60-0-30 mg) combined w i t h i000 mg amoxicillin bid (LAN+AMX) for the first 14 days (n = 30) followed by 30 m g L A N od fill day 28, or a combination 30 mg LAN bid or 90 zg LAN (60-0-30 mg) combined with 500 mg clarith~omycin tid (LAN+CLA) for the same time p e r i o d in = 30). R e s u l t s 18 of 30 p a t i e n t s on LAN+AMX and 21 of 30 on L A N ~ L A so far c o m p l e t e d the study and will be f o l l o w d up. The four week healing rates were 88 % (15/17~ i n the L A N + A M X group and 94 % (17/18) in the L~J+CLA group. The cure rates of HP infection checke{ 4 w e e k s after the end of treatment were 93 % ( 1 4 ~ 5 ) i n the L A N + A M X group and 63 % (10/16) in the L~N+CLA group. Side effects r e s u l t i n g in d i s c o ~ i n u a t i o n of t r e a t m e n t were observed in none of th, p a t i e n t s of the LAN+AMX group, and in 3 p a t i e ~ s of the L A N + C L A group (14.3 %). Conollsion: The authors conclude that the combinatioz of 60 m g L A N d a i l y and 2 g A M X or 1.5 g CLA is a well tolerated and effective treatment r e g i o n for H P e r a d i c a t i o n in DU patients.
E s o p h a g e a l , Gastric, and Duodenal Disorders
A57
EFFECT OF OMEPRAZOLE AND CLARITHROMYCIN PLUS TINIDAZOLE ON THE ERADICATION OF HELICOBACTER PYLORI AND THE RECURRENCE OF DUODENAL ULCER. F.Sazzoli , *S.Gullini , R.M.Zagari, *P.Pazzi, *M.Dalla Libera, P.Pozzato, S.Sottili, S.Fossi, *G.Carli, *R.Scagliarini,P.Simoni and E.Roda. Cattedra di Gastroenterologia, University of Bologna, Bologna, Italy. *Servizio di Gastroenterologia, Ospedale S.Anna, Ferrara, italy. Although it is presently recognized that Helicobacter pylori (H.p.) infection is the main acquired factor in the pathogenesis of duodenal ulcer (DU) disease and that DU patients must be treated with antimicrobials in order to greatly reduce, or even abolish, the dsk of recurrence, a consensus agreement for the optimal therapy (greatest efficacy with least untoward effects and lowest cost) has yet to be accomplished. We have recently reported (Gastroenterology, 1993; 104:A40) that in patients with H.p. gastritis, a short term and low dose therapy with ciarithromycin (C.), omeprazole (O.) and tinidazole (T.) is highly effective for long term eradication and that absence of side effects and good compliance are likely to be major determinants of effectiveness. Aim: in the present study we aimed to investigate the effect of combining one week administration of low dose C. plus T. with a conventional four week healing treatment with O. on the eradication of H.p. in DU patients and on the rate of recurrence of duodenal ulcer. Methods: 171 patients (115 males; 56 females, mean age-+SE 53.9-+1.0 yrs) with active DU and H.p. infection received a 4 weeks administration of O. 20 mg u.i.d. and, during the first week, a combination antimicrobial treatment with C. 250 mg b.Ld. plus T. 500 mg b.i.d.. H.p. infection, as well as eradication or relapse, was established by urease test, histology and 13C-urea breath test (56 pts) or brush c~Gology (115 pts). Upper GI endoscopy with antral biopsies and brush cytology or -urea breath test were performed prior to treatment and at month 1,3,6 and 12 after treatment withdrawl. Drug tolerability was evaluated by patient interview and compliance by pill counting. Results: All, but one single patient who complained of nausea and vomiting, tolerated well and completed the treatment, and took more than 90% of the prescribed medication. At month 1 alter the end of treatment, ulcers were healed in 167 patients and H.p. was eradicated in 158 (94,6%). Follow-up evaluations performed at month 3 (114 pts), 6 (74 pts) and 12 (48 pts) showed persistent eradication and no ulcer recurrence in all cases. Conclusions: One week administration of clarithromycin 250 mg b.i.d, plus tinidazole 500 mg b.i.d, combined with four weeks administration of omeprazole 20 mg u.i.d., is highly effective for long term eradication of H.p. infection also in DU patients, and, in this group of patients, was able to fully abolish ulcer recurrence.
• THE 13C-UREA BREATH TEST FOR EARLY ASSESSMENT OF HELICOBACTER PYLORI ERADICATION. R.M.Zagari, S.Fossi, P.Pozzato, P. Simoni, A.ROda, E. Roda. Cattedra di Gastroenterologia. University of Bologna. Bologna. Italy.
THE laC-UREA BREATH TEST TO EVALUATE THE EFFECT OF ANTISECRETORY DRUGS ON HELICOBACTER PYLORI. R.M.Zagad, P.Pozzato, S.Fossi, P.Simoni, A.Roda, E.ROda. Cattedra di Gastroenterologia. University of Bologna. Bologna. italy.
Introduction. The 13C-urea breath test (lSc-uBT) is an accurate method to non invasively detect the actual presence of Helicobacter pylori (H.p.) infection. For assessment of eradication, 13C-UBT is currently performed, as suggested for other accurate methods such as histology, ureasa test and culture, four weeks after treatment withdrawl in Order to avoid false negative results due to partial suppression of the infection and subsequent recolonization. However there are at lPsresent no studies considering the possibility that an accurate method such as C-UBT could detect true eradication at an earlier stage. Aim. To determine whether ~3C-UBT is capable to assess H.p. eradication earlier than the conventionally adopted four week interval after the end of treatment. Methods. 58 patients (31 males, 27 females; range age 25-69, mean age 48 yrs) with non*ulcer dyspepsia and H.p. infection, parfecipating in an ongoing randomized double blind, double dummy eradication study, underwent upper GI endoscopy and were evaluated by urease test, histology and culture before treatment and four weeks after withdrawing medications. ~3C-UBT was performed (European standard protocol, positive result=excess ~ 13CO2excretion>5 per mil) before treatment and every week for four weeks after withdrawing medications. Results. in 23 out of 58 patients H.p. eradication was established at four weeks after treatment by negative urease test, histology, culture and ~SC-UBT (excess 613CO2 excretion= 1.65_+0.17(mean_+SE) per mil). In all 23 patients in whom eradication was assessed at four weeks after treatment the 13C-UBT was already negative at one week (excess ,~ ~3CO2 excration=1.72-+O.18 (mean+SE)per mil). In all but 3 patients in whom successful eradication was not achieved the 13,C-UBTwas positive since the first week (excess ~ 13CO2excretion = 21.49-+3.22 (mean-+SE) per mil). 3 patients had a negative test at one week (excess ~ 13CO2 excretion= 1.5-+0.7 (mean-C-SE) per nil) which however turned to be positive at the second week evaluation (excess & 13CO2 excretion= 11.5-+2.8 (mean-+SE) per nil) Conclusions: 13C-UBT can assess Helicobacter pylori eradication as soon as one week after treatment withdrawl. When performed at two weeks it shows the same sentivity and specificity of the test performed at four weeks after withdrawing medications.
Introduction. Because of its ability to accurately detect actual Helicobaeter pylori (H.p.) infection, the lSC-urea breath test (lSc-uBT) is a most appreciate method for assessment of eradication after antibacterial treatment. Furthemore since the 13C-UBT is also a quantitative measure of the extent of H.p. colonization, its use during treatment should allow to quantify the progressive reduction of bacterial load. Most of the antibacterial regimens include an aetisecretory drug in order to increase intragastric pH and improve antibiotic availability and absorption. Some of these agents, however, such as omeprazole, are also believed to reduce per se bacterial load thus providing an adjunctive rationale for being included in anti-H.p. combination treatments. Aim. To evaluate, by the 13C- UBT, extent and tim ng of the reduction of H.p. colonization during the sole administration of the proton pump inibitor, omeprazole. Methods. Seven subjects (4 males, 3 females; range age 25-46 yrs, mean age 28 yrs) with H.p. infection, as assessed by 13C-UBT=excess 613CO2 excretion >5 per mil, volunteered the study. Omeprazole 20 mg and 40 mg respectively was administeed for two weeks in a random order, with a four weeks washout period in between, to all subjects. The ~3C-UBT ( according the European Standard Protocol, Eur J Gastroanterol Hepatol 1991; 3:916-21) was performed prior to each treatment period and every other day during treatment and during one + further week after stopping treatment. Results. The mean (_SE) excess ~ 13CO2 excretion was 31.8 (-+3.5) per mil prior to treatment. The maximum decrease was observed at day 3 after both omeprazole dosages (20 mg: excess ~1Sco2 excretion= 19.9_+2.2 (mean_+SE) per nil; 40 mg: excess ~ 13CO2 excretion= 18.9+2.3 (mean-+SE) per mil; 20 mg vs pre-tmatment: p<0.01; 40 mg vs pre-treatment: p<0.Ol; 20 mg 'Is 40 mg: p= ns). The excess ,5 13CO2 excretion returned to pre-treatment values at day 6 after withdrawing treatment. Conclusions. Omeprazole 20 mg/day is capable of reducing excess ~13CO2 excretion by about 40% after three days of administration; increasing the dosage to 40 mg/day does not •mcraase this effect. The partial suppression13ofH.p. Colonization is reverseJ in about one week after treatment withdrawL The C-UBT can be useful to evaluate the effect of different antisecretory agents in reducing H.p. colonization and thus to suggest the optimal agent and its dosage for inclusion in anti-H.p, combination treatments.
D O U B L E - B L I N D T R I A L OF L ~ S O P I ~ Z O L E + P~IOXICILLIN VS. L~NSOPI~ZOLE ÷ CLARITHROMYCIN FOR CURE OF
HELICOBACTER PYLORI INFECTION IN D U O D E N A L ULCER PATIENTS E. BaverdSrffer, H. Schulz, T. Simon, W. HSchter, J. Weingart, H. Porst, E. B~stlein, G.A. Mannes, A. Sommer, H.D. Bundschu, A. Meining, M. Stolte, D e p a r t m e n t of Internal M e d i c i n e II, K l i n i k u m Gro6hadern, U n i v e r s i t y of Munich, and the Ulcer Study Group, Germany. Background: Anti-Helicobacter pylori (HP) treatment u s i n g p r o t o n pump inhibitors and antibiotics is a v e r y promising option. ~im: The aim of the present study was to investigate w h e t h e r combinations of h i g h dose [ansopra2ole (LAN) and antibiotics achieve olinical~y usefull HP cure rates (> 80 %). Methods= 60 patients with an HP-associated duodenal u l c e r (DU) were randomly treated with either ~0 m g L A N bid or 90 mg LAN (60-0-30 mg) combined w i t h i000 mg amoxicillin bid (LAN+AMX) for the first 14 days (n = 30) followed by 30 m g L A N od fill day 28, or a combination 30 mg LAN bid or 90 zg LAN (60-0-30 mg) combined with 500 mg clarith~omycin tid (LAN+CLA) for the same time p e r i o d in = 30). R e s u l t s 18 of 30 p a t i e n t s on LAN+AMX and 21 of 30 on L A N ~ L A so far c o m p l e t e d the study and will be f o l l o w d up. The four week healing rates were 88 % (15/17~ i n the L A N + A M X group and 94 % (17/18) in the L~J+CLA group. The cure rates of HP infection checke{ 4 w e e k s after the end of treatment were 93 % ( 1 4 ~ 5 ) i n the L A N + A M X group and 63 % (10/16) in the L~N+CLA group. Side effects r e s u l t i n g in d i s c o ~ i n u a t i o n of t r e a t m e n t were observed in none of th, p a t i e n t s of the LAN+AMX group, and in 3 p a t i e ~ s of the L A N + C L A group (14.3 %). Conollsion: The authors conclude that the combinatioz of 60 m g L A N d a i l y and 2 g A M X or 1.5 g CLA is a well tolerated and effective treatment r e g i o n for H P e r a d i c a t i o n in DU patients.
E s o p h a g e a l , Gastric, and Duodenal Disorders
A57
EFFECT OF OMEPRAZOLE AND CLARITHROMYCIN PLUS TINIDAZOLE ON THE ERADICATION OF HELICOBACTER PYLORI AND THE RECURRENCE OF DUODENAL ULCER. F.Sazzoli , *S.Gullini , R.M.Zagari, *P.Pazzi, *M.Dalla Libera, P.Pozzato, S.Sottili, S.Fossi, *G.Carli, *R.Scagliarini,P.Simoni and E.Roda. Cattedra di Gastroenterologia, University of Bologna, Bologna, Italy. *Servizio di Gastroenterologia, Ospedale S.Anna, Ferrara, italy. Although it is presently recognized that Helicobacter pylori (H.p.) infection is the main acquired factor in the pathogenesis of duodenal ulcer (DU) disease and that DU patients must be treated with antimicrobials in order to greatly reduce, or even abolish, the dsk of recurrence, a consensus agreement for the optimal therapy (greatest efficacy with least untoward effects and lowest cost) has yet to be accomplished. We have recently reported (Gastroenterology, 1993; 104:A40) that in patients with H.p. gastritis, a short term and low dose therapy with ciarithromycin (C.), omeprazole (O.) and tinidazole (T.) is highly effective for long term eradication and that absence of side effects and good compliance are likely to be major determinants of effectiveness. Aim: in the present study we aimed to investigate the effect of combining one week administration of low dose C. plus T. with a conventional four week healing treatment with O. on the eradication of H.p. in DU patients and on the rate of recurrence of duodenal ulcer. Methods: 171 patients (115 males; 56 females, mean age-+SE 53.9-+1.0 yrs) with active DU and H.p. infection received a 4 weeks administration of O. 20 mg u.i.d. and, during the first week, a combination antimicrobial treatment with C. 250 mg b.Ld. plus T. 500 mg b.i.d.. H.p. infection, as well as eradication or relapse, was established by urease test, histology and 13C-urea breath test (56 pts) or brush c~Gology (115 pts). Upper GI endoscopy with antral biopsies and brush cytology or -urea breath test were performed prior to treatment and at month 1,3,6 and 12 after treatment withdrawl. Drug tolerability was evaluated by patient interview and compliance by pill counting. Results: All, but one single patient who complained of nausea and vomiting, tolerated well and completed the treatment, and took more than 90% of the prescribed medication. At month 1 alter the end of treatment, ulcers were healed in 167 patients and H.p. was eradicated in 158 (94,6%). Follow-up evaluations performed at month 3 (114 pts), 6 (74 pts) and 12 (48 pts) showed persistent eradication and no ulcer recurrence in all cases. Conclusions: One week administration of clarithromycin 250 mg b.i.d, plus tinidazole 500 mg b.i.d, combined with four weeks administration of omeprazole 20 mg u.i.d., is highly effective for long term eradication of H.p. infection also in DU patients, and, in this group of patients, was able to fully abolish ulcer recurrence.
• THE 13C-UREA BREATH TEST FOR EARLY ASSESSMENT OF HELICOBACTER PYLORI ERADICATION. R.M.Zagari, S.Fossi, P.Pozzato, P. Simoni, A.ROda, E. Roda. Cattedra di Gastroenterologia. University of Bologna. Bologna. Italy.
THE laC-UREA BREATH TEST TO EVALUATE THE EFFECT OF ANTISECRETORY DRUGS ON HELICOBACTER PYLORI. R.M.Zagad, P.Pozzato, S.Fossi, P.Simoni, A.Roda, E.ROda. Cattedra di Gastroenterologia. University of Bologna. Bologna. italy.
Introduction. The 13C-urea breath test (lSc-uBT) is an accurate method to non invasively detect the actual presence of Helicobacter pylori (H.p.) infection. For assessment of eradication, 13C-UBT is currently performed, as suggested for other accurate methods such as histology, ureasa test and culture, four weeks after treatment withdrawl in Order to avoid false negative results due to partial suppression of the infection and subsequent recolonization. However there are at lPsresent no studies considering the possibility that an accurate method such as C-UBT could detect true eradication at an earlier stage. Aim. To determine whether ~3C-UBT is capable to assess H.p. eradication earlier than the conventionally adopted four week interval after the end of treatment. Methods. 58 patients (31 males, 27 females; range age 25-69, mean age 48 yrs) with non*ulcer dyspepsia and H.p. infection, parfecipating in an ongoing randomized double blind, double dummy eradication study, underwent upper GI endoscopy and were evaluated by urease test, histology and culture before treatment and four weeks after withdrawing medications. ~3C-UBT was performed (European standard protocol, positive result=excess ~ 13CO2excretion>5 per mil) before treatment and every week for four weeks after withdrawing medications. Results. in 23 out of 58 patients H.p. eradication was established at four weeks after treatment by negative urease test, histology, culture and ~SC-UBT (excess 613CO2 excretion= 1.65_+0.17(mean_+SE) per mil). In all 23 patients in whom eradication was assessed at four weeks after treatment the 13C-UBT was already negative at one week (excess ,~ ~3CO2 excration=1.72-+O.18 (mean+SE)per mil). In all but 3 patients in whom successful eradication was not achieved the 13,C-UBTwas positive since the first week (excess ~ 13CO2excretion = 21.49-+3.22 (mean-+SE) per mil). 3 patients had a negative test at one week (excess ~ 13CO2 excretion= 1.5-+0.7 (mean-C-SE) per nil) which however turned to be positive at the second week evaluation (excess & 13CO2 excretion= 11.5-+2.8 (mean-+SE) per nil) Conclusions: 13C-UBT can assess Helicobacter pylori eradication as soon as one week after treatment withdrawl. When performed at two weeks it shows the same sentivity and specificity of the test performed at four weeks after withdrawing medications.
Introduction. Because of its ability to accurately detect actual Helicobaeter pylori (H.p.) infection, the lSC-urea breath test (lSc-uBT) is a most appreciate method for assessment of eradication after antibacterial treatment. Furthemore since the 13C-UBT is also a quantitative measure of the extent of H.p. colonization, its use during treatment should allow to quantify the progressive reduction of bacterial load. Most of the antibacterial regimens include an aetisecretory drug in order to increase intragastric pH and improve antibiotic availability and absorption. Some of these agents, however, such as omeprazole, are also believed to reduce per se bacterial load thus providing an adjunctive rationale for being included in anti-H.p. combination treatments. Aim. To evaluate, by the 13C- UBT, extent and tim ng of the reduction of H.p. colonization during the sole administration of the proton pump inibitor, omeprazole. Methods. Seven subjects (4 males, 3 females; range age 25-46 yrs, mean age 28 yrs) with H.p. infection, as assessed by 13C-UBT=excess 613CO2 excretion >5 per mil, volunteered the study. Omeprazole 20 mg and 40 mg respectively was administeed for two weeks in a random order, with a four weeks washout period in between, to all subjects. The ~3C-UBT ( according the European Standard Protocol, Eur J Gastroanterol Hepatol 1991; 3:916-21) was performed prior to each treatment period and every other day during treatment and during one + further week after stopping treatment. Results. The mean (_SE) excess ~ 13CO2 excretion was 31.8 (-+3.5) per mil prior to treatment. The maximum decrease was observed at day 3 after both omeprazole dosages (20 mg: excess ~1Sco2 excretion= 19.9_+2.2 (mean_+SE) per nil; 40 mg: excess ~ 13CO2 excretion= 18.9+2.3 (mean-+SE) per mil; 20 mg vs pre-tmatment: p<0.01; 40 mg vs pre-treatment: p<0.Ol; 20 mg 'Is 40 mg: p= ns). The excess ,5 13CO2 excretion returned to pre-treatment values at day 6 after withdrawing treatment. Conclusions. Omeprazole 20 mg/day is capable of reducing excess ~13CO2 excretion by about 40% after three days of administration; increasing the dosage to 40 mg/day does not •mcraase this effect. The partial suppression13ofH.p. Colonization is reverseJ in about one week after treatment withdrawL The C-UBT can be useful to evaluate the effect of different antisecretory agents in reducing H.p. colonization and thus to suggest the optimal agent and its dosage for inclusion in anti-H.p, combination treatments.