Clinical, microbiological, and immunological effects of 3‐ or 7‐day systemic antibiotics adjunctive to subgingival instrumentation in patients with aggressive (Stage III/IV Grade C) periodontitis: A randomized placebo‐controlled clinical trial

Aim To evaluate the clinical non‐inferiority of a 3‐day protocol of systemic antibiotics adjunctive to subgingival instrumentation (SI) compared with a 7‐day‐protocol in patients with Stage III/IV Grade C periodontitis. Materials and Methods Fifty systemically healthy patients (32.7 ± 4.3 years) with aggressive periodontitis (AgP; Stage III/IV Grade C periodontitis) were treated by SI and adjunctive amoxicillin and metronidazole and were randomly assigned to Group A: (n = 25) 500 mg antibiotics (AB) 3 times a day for 3 days, followed by placebo 3 times a day for 4 days, or Group B: (n = 25) 500 mg AB 3 times a day for 7 days. Clinical, microbial, and immunological parameters were assessed at baseline, 3 months, and 6 months, and patient‐related outcomes were assessed after 2 weeks. The primary outcome variable was the number of residual sites with pocket depth (PD) ≥6 mm at 6 months. Results For the primary outcome variable (the number of residual sites with PD ≥6 mm at 6 months), the null hypothesis was rejected and non‐inferiority of the 3‐day AB protocol compared with the 7‐day AB protocol was demonstrated (the upper limits of the 95% confidence interval for intention to treat analysis: [−2.572; 1.050] and per protocol analysis: [−2.523; 1.318] were lower than the assumed margin of Δ = 3.1). Comparable clinical improvements were obtained for all parameters with both antibiotic protocols (p > .05). All investigated periodontopathogens and pro‐inflammatory host‐derived markers were statistically significantly reduced without differences between the treatments (p > .05). Conclusions These findings indicate that in patients with AgP (Stage III/IV Grade C periodontitis), a 3‐day systemic administration of amoxicillin and metronidazole adjunctive to SI may lead to non‐inferior clinical outcomes after 6‐months with fewer adverse events compared with a 7‐day‐protocol.