Clarithromycin (Page 9 of 10)
14.2 Otitis Media
Otitis Media Trial of Clarithromycin vs. Oral Cephalosporin In a controlled clinical trial of pediatric patients with acute otitis media performed in the United States, where significant rates of beta-lactamase producing organisms were found, clarithromycin was compared to an oral cephalosporin. In this trial, strict evaluability criteria were used to determine clinical response. For the 223 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the post-therapy visit was 88% for clarithromycin and 91% for the cephalosporin.
In a smaller number of patients, microbiologic determinations were made at the pre-treatment visit. The presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) are shown in Table 16.
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Pathogen | Clinical Success Rates | |
Clarithromycin | Oral Cephalosporin | |
S. pneumoniae | 13/15 (87%) | 4/5 |
H. influenzae * | 10/14 (71%) | 3/4 |
M. catarrhalis | 4/5 | 1/1 |
S. pyogenes | 3/3 | 0/1 |
All Pathogens Combined | 30/37 (81%) | 8/11 (73%) |
Otitis Media Trials of Clarithromycin vs. Antimicrobial/Beta-lactamase Inhibitor In two other controlled clinical trials of acute otitis media performed in the United States, where significant rates of beta-lactamase producing organisms were found, clarithromycin was compared to an oral antimicrobial agent that contained a specific beta-lactamase inhibitor. In these trials, strict evaluability criteria were used to determine the clinical responses. In the 233 patients who were evaluated for clinical efficacy, the combined clinical success rate (i.e., cure and improvement) at the post-therapy visit was 91% for both clarithromycin and the control.
For the patients who had microbiologic determinations at the pre-treatment visit, the presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) are shown in Table 17.
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Clinical Success Rates | ||
PATHOGEN | Clarithromycin | Antimicrobial/Beta-lactamase Inhibitor |
S. pneumoniae | 43/51 (84%) | 55/56 (98%) |
H. influenzae * | 36/45 (80%) | 31/33 (94%) |
M. catarrhalis | 9/10 (90%) | 6/6 |
S. pyogenes | 3/3 | 5/5 |
All Pathogens Combined | 91/109 (83%) | 97/100 (97%) |
14.3 H. pylori Eradication to Decrease the Risk of Duodenal Ulcer Recurrence
Clarithromycin + Lansoprazole and Amoxicillin Two U.S. randomized, double-blind clinical trials (trial 6 and trial 7) in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an active ulcer within one year) evaluated the efficacy of clarithromycin 500 mg twice daily in combination with lansoprazole 30 mg twice daily and amoxicillin 1 gm twice daily as 14-day triple therapy for eradication of H. pylori.
H. pylori eradication was defined as two negative tests (culture and histology) at 4 weeks to 6 weeks following the end of treatment.
The combination of clarithromycin plus lansoprazole and amoxicillin as triple therapy was effective in eradication of H. pylori (see results in Table 18). Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.
A randomized, double-blind clinical trial (trial 8) performed in the U.S. in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) compared the efficacy of clarithromycin in combination with lansoprazole and amoxicillin as triple therapy for 10 days and 14 days. This trial established that the 10-day triple therapy was equivalent to the 14-day triple therapy in eradicating H. pylori (see results in Table 18).
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Trial | Duration | Triple Therapy Evaluable Analysis * | Triple Therapy Intent-to-Treat Analysis † |
Trial 6 | 14 days | 92 ‡ [80-97.7] (n = 48) | 86 ‡ [73.3-93.5] (n = 55) |
Trial 7 | 14 days | 86 § [75.7-93.6] (n = 66) | 83 § [72-90.8] (n = 70) |
Trial 8 ¶ | 14 days | 85 [77-91] (N = 113) | 82 [73.9-88.1] (N = 126) |
10 days | 84 [76-89.8] (N = 123) | 81 [73.9-87.6] (N = 135) |
Clarithromycin + Omeprazole and Amoxicillin Therapy Three U.S., randomized, double-blind clinical trials in patients with H. pylori infection and duodenal ulcer disease (n = 558) compared clarithromycin plus omeprazole and amoxicillin to clarithromycin plus amoxicillin. Two trials (trials 9 and 10) were conducted in patients with an active duodenal ulcer, and the third trial (trial 11) was conducted in patients with a duodenal ulcer in the past 5 years, but without an ulcer present at the time of enrollment. The dosage regimen in the trials was clarithromycin 500 mg twice a day plus omeprazole 20 mg twice a day plus amoxicillin 1 gram twice a day for 10 days. In trials 9 and 10, patients who took the omeprazole regimen also received an additional 18 days of omeprazole 20 mg once a day. Endpoints studied were eradication of H. pylori and duodenal ulcer healing (trials 9 and 10 only). H. pylori status was determined by CLOtest ® , histology, and culture in all three trials. For a given patient, H. pylori was considered eradicated if at least two of these tests were negative, and none was positive. The combination of clarithromycin plus omeprazole and amoxicillin was effective in eradicating H. pylori (see results in Table 19).
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Clarithromycin + omeprazole + amoxicillin | Clarithromycin + amoxicillin | |||
Per-Protocol * | Intent-to-Treat † | Per-Protocol * | Intent-to-Treat † | |
Trial 9 | ‡77 [64, 86] (n = 64) | 69 [57, 79] (n = 80) | 43 [31, 56] (n = 67) | 37 [27, 48] (n = 84) |
Trial 10 | ‡78 [67, 88] (n = 65) | 73 [61, 82] (n = 77) | 41 [29, 54] (n = 68) | 36 [26, 47] (n = 84) |
Trial 11 | ‡90 [80, 96] (n = 69) | 83 [74, 91] (n = 84) | 33 [24, 44] (n = 93) | 32 [23, 42] (n = 99) |
Clarithromycin + Omeprazole Therapy
Four randomized, double-blind, multi-center trials (trials 12, 13, 14, and 15) evaluated clarithromycin 500 mg three times a day plus omeprazole 40 mg once a day for 14 days, followed by omeprazole 20 mg once a day (trials 12, 13, and 15) or by omeprazole 40 mg once a day (trial 14) for an additional 14 days in patients with active duodenal ulcer associated with
H. pylori. Trials 12 and 13 were conducted in the U.S. and Canada and enrolled 242 and 256 patients, respectively.
H. pylori infection and duodenal ulcer were confirmed in 219 patients in trial 12 and 228 patients in trial 13. These trials compared the combination regimen to omeprazole and clarithromycin monotherapies. Trials 14 and 15 were conducted in Europe and enrolled 154 and 215 patients, respectively.
H. pylori infection and duodenal ulcer were confirmed in 148 patients in trial 14 and 208 patients in trial 15. These trials compared the combination regimen to omeprazole monotherapy. The results for the efficacy analyses for these trials are described in Tables 20, 21, and 22.
Duodenal Ulcer Healing The combination of clarithromycin and omeprazole was as effective as omeprazole alone for healing duodenal ulcer (see Table 20).
Trial | Clarithromycin + Omeprazole | Omeprazole | Clarithromycin |
U.S. Trials | |||
Trial 13 | 94% (58/62) * | 88% (60/68) | 71% (49/69) |
Trial 12 | 88% (56/64) * | 85% (55/65) | 64% (44/69) |
Non-U.S. Trials | |||
Trial 15 | 99% (84/85) | 95% (82/86) | N/A |
Trial 14 † | 100% (64/64) | 99% (71/72) | N/A |
Eradication of H. pylori Associated with Duodenal Ulcer The combination of clarithromycin and omeprazole was effective in eradicating H. pylori (see Table 21). H. pylori eradication was defined as no positive test (culture or histology) at 4 weeks following the end of treatment, and two negative tests were required to be considered eradicated. In the per-protocol analysis, the following patients were excluded: dropouts, patients with major protocol violations, patients with missing H. pylori tests post-treatment, and patients that were not assessed for H. pylori eradication at 4 weeks after the end of treatment because they were found to have an unhealed ulcer at the end of treatment.
Trial | Clarithromycin + Omeprazole | Omeprazole | Clarithromycin |
U.S. Trials | |||
Trial 13 | 0% (0/59) | 39% (17/44) | |
Trial 12 | 0% (0/54) | 31% (13/42) | |
Non-U.S. Trials | |||
Trial 15 | 74% (64/86) * | 1% (1/90) | N/A |
Trial 14 | 83% (50/60) * | 1% (1/74) | N/A |
Duodenal Ulcer Recurrence Ulcer recurrence at 6-months and at 12 months following the end of treatment was assessed for patients in whom ulcers were healed post-treatment (see the results in Table 22). Thus, in patients with duodenal ulcer associated with H. pylori infection, eradication of H. pylori reduced ulcer recurrence.
H. pylori Negative at 4-6 Weeks | H. pylori Positive at 4-6 Weeks | |
U.S. Trials Recurrence at 6 Months | ||
Trial 100 | ||
Clarithromycin + Omeprazole | 6% (2/34) | 56% (9/16) |
Omeprazole | (0/0) | 71% (35/49) |
Clarithromycin | 12% (2/17) | 32% (7/22) |
Trial 067 | ||
Clarithromycin + Omeprazole | 38% (11/29) | 50% (6/12) |
Omeprazole | (0/0) | 67% (31/46) |
Clarithromycin | 18% (2/11) | 52% (14/27) |
Non-U.S. Trials Recurrence at 6 Months | ||
Trial 058 | ||
Clarithromycin + Omeprazole | 6% (3/53) | 24% (4/17) |
Omeprazole | 0% (0/3) | 55% (39/71) |
Trial 812b | ||
Clarithromycin + Omeprazole | 5% (2/42) | 0% (0/7) |
Omeprazole | 0% (0/1) | 54% (32/59) |
Non-U.S. Trials Recurrence at 12-Months in Trial 14 | ||
Clarithromycin + Omeprazole | 3% (1/40) | 0% (0/6) |
Omeprazole | 0% (0/1) | 67% (29/43) |
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