- Email: [email protected]
Potential value of Helicobacter pylori serodiagnosis
April 1995
Q LARGE TRIAL COMPARES LANSOPRAZOLE TO OMEPRAZOLE DO Castell, JE Richter, M Robinson, S Sontag. The Graduate Hospital, Philadelphia, PA; University of Alabama, Birmingham, AL; Oklahoma Foundation for Digestive Research, Oklahoma City, OK; Hines VA Hospital, Hines, IL. Lansoprazole (LAN) 30 mg a n d l 5 mg QD were compared to omeprazole (OME) 20 mg QD and placebo (PBO) in patients with endoscopically proven erosive reflux esophagitis (RE) in a randomized, double-blind, multicenter clinical trial. Forty-four (44) investigators enrolled 1284 patients (836 males/448 females): LAN 30 rag: 422 patients, LAN 15 mg: 218 patients, OME 20 rag: 431 patients, PBO: 213 patients. Study medication was taken each day for eight weeks. Endoscopies were performed at baseline, weeks 2, 4 and 8 (and week 6 if not healed at week 2 and week 4). Results: LAN 30 mg was as effective as r~nt~ e ofNi htswitha e ~ m OME 20 mg and both were more effective ~w,,.~L ~,~,,,o~ (p<0~05) than LAN 15 mg in healing acuteerosive RE (week 8 healing rates for evaluahle patients: LAN 30 rag: 90.9%, OME 20 mg: 90.7%, LAN 15 rag: ~ 78.8%). After just one dose, significantly fewer LAN 30 mg patients reported episodes of day and night heartburn (p=0.001 and p=0.005, respectively) and had lower severity of pain associated with reported day and LAN30 LANI5 OME20 night heartbum than OME 20 mg patients. • sigllificantl superiorto OME20mg After eight weeks of treatment, LAN 30 =d LAN1 ~m$at p<0.OS. mg patients had experienced significantly fewer episodes of night heartburn (see figure) and significantly less severe night heartburn than both OME 20 mg and LAN 15 mgpatients. Similar proportions of patients in each of the four treatment groups reported possibly or probably treatment-related adverse events. The most frequently reported treatment-related adverse events (> 2% occurrence) were headache, diarrhea, and nausea. As expected, fasting serum gastrin levels increased significantly from baseline in all active-treatment groups; however, median fasting serum gastrin levels remained within normal limits for all treatment groups. Conclusion: LAN 30 mg QD provided faster heartburn reliefthan OME 20 mg Q D and is as safe and effective as OME 20 mg QD in healing erosive RE. This research was funded by TAP Pharmaceuticals Inc., Deerfield, IL.
P O T E N T I A L V A L U E OF H E L I C O B A C T E R PYLORI S E R O D I A G N O SIS. F. Catalano, G. Branciforte, R. Catanzaro, A. Liberti, C. Bentivegna, A. Brogna, A. Blasi. Dept of Internal Medicine. G a s t r o e n t e r o l o g y Unit. Univ e r s i t y of Catania. Italy. Soon a f t e r the o r i g i n a l i s o l a t i o n of H e l i c o b a c t e r pylori (HP) it b e c a m e o b v i o u s t h a t there was a sys t e m i c i m m u n e r e s p o n s e in c o l o n i z e d s u b j e c t s . Using indirect enzyme,linked immunosorbent assay test (ELISA) m a n y autors h a v e d e m o n s t r a t e d a h i g h degree of c o r r e l a t i o n b e t w e e n the p r e s e n c e of serum a n t i b o d i e s a g a i n s t HP and g a s t r i c infection by this bacterium. In t h i s study we tested the possible e x i s t e n c e of a s t a t i s t i c a l l y s i g n i f i c a n t diff e r e n c e in s e r u m l e v e l s of I g G a n t i H P in H P + v e normal s u b j e c t s (N), in H P + v e d u o d e n a l u l c e r p t s (DU) and HP+ve g a s t r i t i s pts (G). We selected 42 N pts (20 M - 22 F; range 20 - 72, m e a n age 43.71), 43 DU p t s (31 M - 12 F; r a n g e 20 - 74, m e a n a g e 46.88) and 24 G p t s (12 M - 12 F; range 30 - 83, m e a n a g e 57.50). H P p o s i t i v i t y w a s t e s t e d using urease-test, microscopy and culture. We studied serum l e v e l s of IgG c l a s s of all pts u s i n g E L I S A method (Helori-test Eurospital). IgG s e r u m level mean was 53.36 ± 19.31 U£urospitat in N, 63.77 ± 31.08 UEurospitat in DU p t s a n d 49.87 ± 19 .83 U£urospitat in G pts (n.v. : < 30 UEuros~itat). A n o t - s i g n i f i c a n t difference was found among the three groups. We conclude that s e r o d i a g n o s i s of HP using ELISA m e t h o d is u s e f u l as a s c r e e n i n g of H P p o s i t i v i t y but not p r e d i c t o r of u p p e r g a s t r o i n t e s t i n a l e n d o s c o p y results.
Esophageal, Gastric, and Duodenal Disorders
A67
• HP P O S I T I V E F U N C T I O N A L D Y S P E P S I A IN E L D E R L Y PATIENTS: C O M P A R I S O N OF TWO TREATMENTS. F. catalano, °R. T e r r a n o v a , A. Brogna, G. B r a n c i f o r t e , R. Catanzaro, A. Liberti, C. Bentivegna, *S. Luca. Dept of Internal Medicine. G a s t r o e n t e r o l o g y Unit. *Geriatric Dept. U n i v e r s i t y of Catania. Italy. Although Helicobacter p y l o r i (HP) a p p e a r s to be the p r i m a r y c a u s e of h i s t o l o g i c a l g a s t r i t i s , its role in functional d y s p e p s i a (FD) has b e e n controversial. A p p r o x i m a t e l y 50% of p a t i e n t s w i t h FD have h i s t o l o g i c g a s t r i t i s and HP infection, p a r t i c u larly if t h e y are elderly. If H P is of e t i o l o g i c importance in FD, t h e n e r a d i c a t i o n of the o r g a n i s m from the g a s t r i c m u c o s a w o u l d be e x p e c t e d to results in an improvement in d y s p e p t i c symptoms. In t h i s s t u d y we v e r i f i e d t h e e f f e c t i v e n e s s of t h e a s s o c i a t i o n of b i s m u t h s a l t s 240 mg b . i . d , p l u s metronidazole 250 m g t.i.d, a n d a m o x i c i l l i n 1 g b.i.d, for 2 w e e k s (A group) vs o m e p r a z o l e 20 mg daily for 4 weeks plus a m o x i c i l l i n 1 g b.i.d, for 2 weeks (E group) on HP e r a d i c a t i o n and on the imp r o v e m e n t of H P r e l a t e d d y s p e p t i c s y m p t o m s . W e randomlyassigned 154 FD HP+ve e l d e r l y pts to two d i f f e r e n t t r e a t m e n t groups: A group (81 pts, 44 M37 F; r a n g e 59 - 81 y r s ; m e a n a g e 68.4) a n d B g r o u p (73 pts, 33 M - 40 F; r a n g e 61 - 82 yrs; mean age 69.9). HP p o s i t i v i t y was assessed by testing 3 a n t r a l and b o d y b i o p s y s p e c i m e n s as foll o w s : urease-test, m i c r o s c o p y and culture. Histology w a s p e r f o r m e d u s i n g h a e m a t o x y l i n and eosin stain. T w o m o n t h s a f t e r the end of t h e r a p y 7 6 / 8 1 (93.8%) pts in the A g r o u p and 70/73 (95.8%) p t s in the B g r o u p p r e s e n t e d t h e m s e l v e s for control. HP w a s e r a d i c a t e d in 6 3 / 7 6 (82.9%) p t s i n the A g r o u p a n d 5 7 / 7 0 (81.4%) p t s in t h e B g r o u p . A l l eradicated pts showed improvement in s y m p t o m a t o l o gy and in g a s t r i t i s a c t i v i t y ; no r e m a r k a b l e side effects were referred. In c o n c l u s i o n the two ~ treatments are e f f e c t i v e in the HP e r a d i c a t i o n and in the improvement of s y m p t o m a t o l o g y and h i s t o l o g y in e l d e r l y p t s (Chi 2 , p< 0.001). No s i g n i f i c a n t difference b e t w e e n the two groups was recorded.
LANSOPRAZOLE - ALTERNATIVE METHOD OF ADMINISTRATION OF GRANULES ZIg Cavanaugh, CJ. Eason, H.H. Shi atwl IL I-ZC. Chun Abbott Laboratories, Abbott Park, IL
Lansoprazole (PREVACID) is a proton pomp inhibitor which is well tolerated and provides safe and effective treatment of duodenal and gastric ulcer, reflux esophagitis (RE) and Zollinger-Ellison syndrome and maintenance of RE. The marketed formulation of lansoprazole consists of a capsule containing enteric coated granules. Since some patients may be unable to swallow a capsule formulation, a study was conducted to assess the bioavallabinty of the granules administered in a soft food preparation, a spoonful of applesauce. A single--dose, fasting, two--period complete-crossover study was condocted in 24 heelthy, nonsmoking adult male subjects. Halfofthe subjects received Regimen A (granules from a 30 nag capsule placed in a tablespoonful of applesauce) and the other half received Regimen B (intuet 30 mg capsule) during Period 1 of the crossover study. The regimens were reversed during Period 2, one week later. Blood samples were obtained over 12 hours and pharmacokinetle parameters were determined. No statistically significant differences (0.05 level) in Tmax, Cn,~x, and AUCo..~were detected between regimens. Pharmaeokinetie Parameters (n=23 subjects) Tm~x Cm~x ht2 p AUCo.,,o (hours) (ng/mL) (hours) (l/hour) (ng.h/mL) Regimen A Mean 1.8 696 1.21 0.647 1956 SD 0.7 250 0.45 0.217 1129 %CV 39 36 37 34 58 Min 1.0 400 0.66 0.288 671 Max 3.0 1216 2.41 1.050 4909 Regimen B Mean 1.7 800 1.23 0.629 2090 SD 0.8 323 0.44 0.210 1164 %CV 49 40 36 33 56 Min 1.0 291 0.64 0.286 598 Max 4.0 1338 2.43 1.085 5120 These data indicate similar bioavailability between the two regimens. Lansoprazole granules contained in a standard capsule dosage formulation may be removed and placed directly into applesauce and administered to appropriate patients.
Q LARGE TRIAL COMPARES LANSOPRAZOLE TO OMEPRAZOLE DO Castell, JE Richter, M Robinson, S Sontag. The Graduate Hospital, Philadelphia, PA; University of Alabama, Birmingham, AL; Oklahoma Foundation for Digestive Research, Oklahoma City, OK; Hines VA Hospital, Hines, IL. Lansoprazole (LAN) 30 mg a n d l 5 mg QD were compared to omeprazole (OME) 20 mg QD and placebo (PBO) in patients with endoscopically proven erosive reflux esophagitis (RE) in a randomized, double-blind, multicenter clinical trial. Forty-four (44) investigators enrolled 1284 patients (836 males/448 females): LAN 30 rag: 422 patients, LAN 15 mg: 218 patients, OME 20 rag: 431 patients, PBO: 213 patients. Study medication was taken each day for eight weeks. Endoscopies were performed at baseline, weeks 2, 4 and 8 (and week 6 if not healed at week 2 and week 4). Results: LAN 30 mg was as effective as r~nt~ e ofNi htswitha e ~ m OME 20 mg and both were more effective ~w,,.~L ~,~,,,o~ (p<0~05) than LAN 15 mg in healing acuteerosive RE (week 8 healing rates for evaluahle patients: LAN 30 rag: 90.9%, OME 20 mg: 90.7%, LAN 15 rag: ~ 78.8%). After just one dose, significantly fewer LAN 30 mg patients reported episodes of day and night heartburn (p=0.001 and p=0.005, respectively) and had lower severity of pain associated with reported day and LAN30 LANI5 OME20 night heartbum than OME 20 mg patients. • sigllificantl superiorto OME20mg After eight weeks of treatment, LAN 30 =d LAN1 ~m$at p<0.OS. mg patients had experienced significantly fewer episodes of night heartburn (see figure) and significantly less severe night heartburn than both OME 20 mg and LAN 15 mgpatients. Similar proportions of patients in each of the four treatment groups reported possibly or probably treatment-related adverse events. The most frequently reported treatment-related adverse events (> 2% occurrence) were headache, diarrhea, and nausea. As expected, fasting serum gastrin levels increased significantly from baseline in all active-treatment groups; however, median fasting serum gastrin levels remained within normal limits for all treatment groups. Conclusion: LAN 30 mg QD provided faster heartburn reliefthan OME 20 mg Q D and is as safe and effective as OME 20 mg QD in healing erosive RE. This research was funded by TAP Pharmaceuticals Inc., Deerfield, IL.
P O T E N T I A L V A L U E OF H E L I C O B A C T E R PYLORI S E R O D I A G N O SIS. F. Catalano, G. Branciforte, R. Catanzaro, A. Liberti, C. Bentivegna, A. Brogna, A. Blasi. Dept of Internal Medicine. G a s t r o e n t e r o l o g y Unit. Univ e r s i t y of Catania. Italy. Soon a f t e r the o r i g i n a l i s o l a t i o n of H e l i c o b a c t e r pylori (HP) it b e c a m e o b v i o u s t h a t there was a sys t e m i c i m m u n e r e s p o n s e in c o l o n i z e d s u b j e c t s . Using indirect enzyme,linked immunosorbent assay test (ELISA) m a n y autors h a v e d e m o n s t r a t e d a h i g h degree of c o r r e l a t i o n b e t w e e n the p r e s e n c e of serum a n t i b o d i e s a g a i n s t HP and g a s t r i c infection by this bacterium. In t h i s study we tested the possible e x i s t e n c e of a s t a t i s t i c a l l y s i g n i f i c a n t diff e r e n c e in s e r u m l e v e l s of I g G a n t i H P in H P + v e normal s u b j e c t s (N), in H P + v e d u o d e n a l u l c e r p t s (DU) and HP+ve g a s t r i t i s pts (G). We selected 42 N pts (20 M - 22 F; range 20 - 72, m e a n age 43.71), 43 DU p t s (31 M - 12 F; r a n g e 20 - 74, m e a n a g e 46.88) and 24 G p t s (12 M - 12 F; range 30 - 83, m e a n a g e 57.50). H P p o s i t i v i t y w a s t e s t e d using urease-test, microscopy and culture. We studied serum l e v e l s of IgG c l a s s of all pts u s i n g E L I S A method (Helori-test Eurospital). IgG s e r u m level mean was 53.36 ± 19.31 U£urospitat in N, 63.77 ± 31.08 UEurospitat in DU p t s a n d 49.87 ± 19 .83 U£urospitat in G pts (n.v. : < 30 UEuros~itat). A n o t - s i g n i f i c a n t difference was found among the three groups. We conclude that s e r o d i a g n o s i s of HP using ELISA m e t h o d is u s e f u l as a s c r e e n i n g of H P p o s i t i v i t y but not p r e d i c t o r of u p p e r g a s t r o i n t e s t i n a l e n d o s c o p y results.
Esophageal, Gastric, and Duodenal Disorders
A67
• HP P O S I T I V E F U N C T I O N A L D Y S P E P S I A IN E L D E R L Y PATIENTS: C O M P A R I S O N OF TWO TREATMENTS. F. catalano, °R. T e r r a n o v a , A. Brogna, G. B r a n c i f o r t e , R. Catanzaro, A. Liberti, C. Bentivegna, *S. Luca. Dept of Internal Medicine. G a s t r o e n t e r o l o g y Unit. *Geriatric Dept. U n i v e r s i t y of Catania. Italy. Although Helicobacter p y l o r i (HP) a p p e a r s to be the p r i m a r y c a u s e of h i s t o l o g i c a l g a s t r i t i s , its role in functional d y s p e p s i a (FD) has b e e n controversial. A p p r o x i m a t e l y 50% of p a t i e n t s w i t h FD have h i s t o l o g i c g a s t r i t i s and HP infection, p a r t i c u larly if t h e y are elderly. If H P is of e t i o l o g i c importance in FD, t h e n e r a d i c a t i o n of the o r g a n i s m from the g a s t r i c m u c o s a w o u l d be e x p e c t e d to results in an improvement in d y s p e p t i c symptoms. In t h i s s t u d y we v e r i f i e d t h e e f f e c t i v e n e s s of t h e a s s o c i a t i o n of b i s m u t h s a l t s 240 mg b . i . d , p l u s metronidazole 250 m g t.i.d, a n d a m o x i c i l l i n 1 g b.i.d, for 2 w e e k s (A group) vs o m e p r a z o l e 20 mg daily for 4 weeks plus a m o x i c i l l i n 1 g b.i.d, for 2 weeks (E group) on HP e r a d i c a t i o n and on the imp r o v e m e n t of H P r e l a t e d d y s p e p t i c s y m p t o m s . W e randomlyassigned 154 FD HP+ve e l d e r l y pts to two d i f f e r e n t t r e a t m e n t groups: A group (81 pts, 44 M37 F; r a n g e 59 - 81 y r s ; m e a n a g e 68.4) a n d B g r o u p (73 pts, 33 M - 40 F; r a n g e 61 - 82 yrs; mean age 69.9). HP p o s i t i v i t y was assessed by testing 3 a n t r a l and b o d y b i o p s y s p e c i m e n s as foll o w s : urease-test, m i c r o s c o p y and culture. Histology w a s p e r f o r m e d u s i n g h a e m a t o x y l i n and eosin stain. T w o m o n t h s a f t e r the end of t h e r a p y 7 6 / 8 1 (93.8%) pts in the A g r o u p and 70/73 (95.8%) p t s in the B g r o u p p r e s e n t e d t h e m s e l v e s for control. HP w a s e r a d i c a t e d in 6 3 / 7 6 (82.9%) p t s i n the A g r o u p a n d 5 7 / 7 0 (81.4%) p t s in t h e B g r o u p . A l l eradicated pts showed improvement in s y m p t o m a t o l o gy and in g a s t r i t i s a c t i v i t y ; no r e m a r k a b l e side effects were referred. In c o n c l u s i o n the two ~ treatments are e f f e c t i v e in the HP e r a d i c a t i o n and in the improvement of s y m p t o m a t o l o g y and h i s t o l o g y in e l d e r l y p t s (Chi 2 , p< 0.001). No s i g n i f i c a n t difference b e t w e e n the two groups was recorded.
LANSOPRAZOLE - ALTERNATIVE METHOD OF ADMINISTRATION OF GRANULES ZIg Cavanaugh, CJ. Eason, H.H. Shi atwl IL I-ZC. Chun Abbott Laboratories, Abbott Park, IL
Lansoprazole (PREVACID) is a proton pomp inhibitor which is well tolerated and provides safe and effective treatment of duodenal and gastric ulcer, reflux esophagitis (RE) and Zollinger-Ellison syndrome and maintenance of RE. The marketed formulation of lansoprazole consists of a capsule containing enteric coated granules. Since some patients may be unable to swallow a capsule formulation, a study was conducted to assess the bioavallabinty of the granules administered in a soft food preparation, a spoonful of applesauce. A single--dose, fasting, two--period complete-crossover study was condocted in 24 heelthy, nonsmoking adult male subjects. Halfofthe subjects received Regimen A (granules from a 30 nag capsule placed in a tablespoonful of applesauce) and the other half received Regimen B (intuet 30 mg capsule) during Period 1 of the crossover study. The regimens were reversed during Period 2, one week later. Blood samples were obtained over 12 hours and pharmacokinetle parameters were determined. No statistically significant differences (0.05 level) in Tmax, Cn,~x, and AUCo..~were detected between regimens. Pharmaeokinetie Parameters (n=23 subjects) Tm~x Cm~x ht2 p AUCo.,,o (hours) (ng/mL) (hours) (l/hour) (ng.h/mL) Regimen A Mean 1.8 696 1.21 0.647 1956 SD 0.7 250 0.45 0.217 1129 %CV 39 36 37 34 58 Min 1.0 400 0.66 0.288 671 Max 3.0 1216 2.41 1.050 4909 Regimen B Mean 1.7 800 1.23 0.629 2090 SD 0.8 323 0.44 0.210 1164 %CV 49 40 36 33 56 Min 1.0 291 0.64 0.286 598 Max 4.0 1338 2.43 1.085 5120 These data indicate similar bioavailability between the two regimens. Lansoprazole granules contained in a standard capsule dosage formulation may be removed and placed directly into applesauce and administered to appropriate patients.