TABLE 2.
Adverse side effects, clinical efficacies, and symptomatic responses according to amoxicillin-clavulanate treatment regimena
| Outcome measure | Values for indicated treatment group and A/C treatment regimen |
|||
|---|---|---|---|---|
| Historical controls (90 amoxicillin/6.4 mg clavulanate/kg/day × 10 days) (n = 401) | Phase 1 children (90 amoxicillin/3.2 mg clavulanate/kg/day × 10 days) (n = 40) | Phase 2 children (80 amoxicillin/2.85 mg clavulanate/kg/day × 10 days) (n = 72) | P value | |
| Adverse effects of study medication | ||||
| Occurrence of PDDb—no. of children (%) | 104 (26) | 10 (25) | 12 (17) | 0.10c |
| No. days until 15% of parents reported PDD | 4 days | 4 days | 6 days | 0.16d |
| Peak time with PDD; no. of children with PDD/total no. of children (%) | Day 6; 64/394 (16) | Days 5 & 6; 8/39 (20) | Day 6; 12/68 (18) | N/A |
| No. of days with PDD—mean ± SD (no. of children with data) | 1.1 ± 2.2 (401) | 1.3 ± 2.6 (39) | 1.1 ± 2.7 (68) | 0.88e |
| Occurrence of diaper dermatitis—no. of children (%) | 134 (33) | 10 (25) | 15 (21) | 0.04c |
| Discontinued study medication because of diarrhea and/or diaper dermatitisf—no. of children (%) | 39 (10) | 2 (5) | 1 (1) | <0.05c |
| Discontinued temporarily | 32 (8) | 2 (5) | 1 (1) | |
| Discontinued permanently | 7 (2) | 0 | 0 | |
| Clinical failure—proportion of children (%) (95% CI) | 62/380 (16) (13 to 20) | 4/35 (11) (1 to 22) | 8/64 (12) (4 to 21) | 0.44c |
| AOM-SOS score from day 1 to day 7—mean ± SD (no. of children) | ||||
| All children | 2.4 ± 1.6 (367) | 2.7 ± 1.4 (36) | 2.2 ± 1.7 (59) | 0.32g |
| Children who experienced clinical success | 2.4 ± 1.6 (304) | 2.5 ± 1.2 (29) | 2.3 ± 1.7 (49) | 0.52g |
| Children who experienced clinical failure | 2.7 ± 1.7 (56) | 4.3 ± 1.8 (4) | 1.7 ± 1.8 (7) | 0.58g |
| Decrease of >50% in AOM-SOS score from baseline to the end-of-treatment assessment—no. of children with decrease/total no. of children (%)h | ||||
| All children | 320/362 (88) | 30/35 (86) | 57/64 (89) | 0.88c |
| Children who experienced clinical success | 280/308 (91) | 28/31 (90) | 52/56 (93) | 0.66c |
| Children who experienced clinical failure | 40/54 (74) | 2/4 (50) | 5/8 (62) | 0.66c |
| Parents' stated level of satisfaction with child's therapy at end-of-treatment visit—mean ± SD (no. of children)i | 4.47 ± 0.88 (371) | 4.69 ± 0.72 (35) | 4.75 ± 0.76 (4) | 0.02e |
Data were missing for some children for some analyses. CI, confidence interval. N/A, not applicable. SD, standard deviation.
PDD, protocol-defined diarrhea.
Comparison of historical controls to phase 2 children, logistic regression.
Comparison of historical controls to phase 2 children, log rank test.
Comparison of historical controls to phase 2 children, t test.
Study medication was discontinued only because of diaper dermatitis in 2 children.
Comparison of historical controls to phase 2 children, generalized estimated equations.
The AOM-SOS scale consists of five discrete items—tugging of ears, crying, irritability, difficulty sleeping, and fever. Parents are asked to rate these symptoms, in comparison with the child's usual state, as “none,” “a little,” or “a lot,” with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. Data are restricted to children with an AOM-SOS score of ≥3 at enrollment. The cutoff between ≤50% and >50% was based on data from a study of minimal important difference in AOM-SOS scores (12).
Levels of satisfaction were scored on the following scale: 1, very dissatisfied; 2, somewhat dissatisfied; 3, neutral; 4, somewhat satisfied; 5, very satisfied.