Clinical efficacy of hydrogen peroxide-based mouthwash versus chlorhexidine in post-periodontal flap surgery healing: a randomized controlled clinical trial

Abstract Background Postsurgical wound healing following periodontal flap surgery is critical for achieving optimal clinical outcomes. While chlorhexidine (CHX) remains the gold standard antiseptic mouthwash, concerns regarding adverse effects have prompted the exploration of alternative agents. A novel hydrogen peroxide-based formulation containing lactoferrin and zinc lactate may offer comparable efficacy with improved safety profiles. Methods To compare the clinical efficacy of a hydrogen peroxide-based mouthwash (Freshchlor Plus-Group Pharmaceuticals India) containing 0.1% H₂O₂, 0.05% lactoferrin, and 0.14% zinc lactate versus 0.12% chlorhexidine (Group Pharmaceuticals India) on wound healing outcomes, patient-reported outcome measures (PROMs), and adverse reactions following periodontal flap surgery.This single-center, randomized, double-blind, parallel-design clinical trial included 32 systemically healthy adults who underwent periodontal flap surgery. Participants were randomly allocated to either Group A (0.12% CHX, n = 16) or Group B (Freshchlor Plus, n = 16). Both groups were rinsed with 10 mL of the assigned mouthwash for 60 s twice daily for 14 days. Primary outcomes included Wound Healing Index (WHI) scores assessed on days 3, 7, and 14. Secondary outcomes included pain intensity measured using the visual analogue scale (VAS), analgesic consumption, and adverse reactions. Statistical analyses included the Mann‒Whitney U test, chi‒square test, and descriptive statistics, with significance set at p < 0.05. Results Both groups demonstrated excellent wound healing, with no statistically significant differences in WHI scores on day 3 (Group A: 1.25 ± 0.58 vs. Group B: 1.07 ± 0.250; p = 0.325), day 7 (Group A: 1.19 ± 0.54 vs. Group B: 1.07 ± 0.26; p = 0.59), or day 14 (both groups: 1.00 ± 0.000). Pain levels remained minimal in both groups, with 96.9% of participants reporting VAS scores of 0–4 mm at all time points. Analgesic consumption was comparable between the groups ( p = 0.545). However, adverse reactions differed significantly ( p = 0.046), with Group B exhibiting fewer adverse events (6.2% vs. 37.5%). Notably, tooth staining occurred exclusively in Group A (31.3%). Conclusion The hydrogen peroxide-, lactoferrin-, and zinc-containing mouthwash demonstrated favorable early postoperative healing and was associated with fewer reported adverse effects than 0.12% chlorhexidine, while no significant between-group difference was observed in the primary wound-healing outcome. These findings suggest that the formulation may be a promising alternative for short-term postoperative oral care following periodontal flap surgery; however, larger, adequately powered multicenter trials with longer follow-up and objective microbiological and adherence assessments are needed to confirm these findings. Trial Registration Clinical Trials Registry-India (CTRI), CTRI/2025/10/096090, registered on 15 October 2025. Prospectively registered.