Results of chronic anal fissure treatment with botulinum toxin type A at a dose (dosage) of 80 units without its incision (single-center prospective randomized controlled trial NCT05598164)

AIM: to assess efficacy of botulinum toxin type A (BTA) at a dosage of 80 units for chronic anal fissure (CAF) without excision.

PATIENTS AND METHODS: single-center prospective randomized controlled trial (NCT05598164) was held between September 2022 and December 2024 in order to compare isolated usage of BTA (main group) at a dosage of 80 units with its combination with excision of the fissure — BTA + EF (control group) for CAF. One hundred sixty-seven were randomized — 86 were included in main group and 81 — in control one. After application of exclusion criteria 126 patients were included in final analysis: 65 in group of BTA only and 61 in group of its combination with EF. Control examination, pain syndrome intensity according to visual-analogue scale (VAS), profilometry and assessment of transitory anal incontinence according to Wexner scale were done in pre- and postoperative period. The primary endpoint was epithelization of defect (for the main group) or postoperative wound (for the control group) on 60th day after surgery.

RESULTS: on the 60th day postoperative defect healed in 46/59 (78.0%; 95% confidence interval (CI): 65.2–87.7) patients in main group vs. 34/50 (68.0%; 95% CI: 53.3 — 80.5) patients for postoperative wound in control group (р = 0.3). At the same time, on the 15th day defect healed in 12/65 (18.4%) patients in BTA group, whereas no one's postoperative wound healed in group BTA + EF (р = 0.0003); on the 30th day — in 18/59 (30.5%) vs. 1/53 (1.9%) patients(р < 0,0001); on the 45th day — in 31/57 (54.4%) vs. 3/52 (5.8%) patients(р < 0.0001). The rate of postoperative complications was 23/65 (35.4%) in main group and 23/61 (37.7%) in controls (р = 0.8). On the 30th day transitory anal incontinence was detected in 15/60 (25.0%) patients in BTA group and in 18/53 (34.0%) in combinations of its injection with EF (p = 0.3); on the 60th day — in 7/60 (11.7%) and 9/51 (17.6%) patients (p = 0.4); external hemorrhoids thrombosis developed in 2/65 (3.1%) patients of main group and in 2/61 (3.3%) of control group (p = 1.0); intrasphincter fistula — in 5/60 (8.3%) and 3/50 (6.0%) patients (p = 0.7). Intensity of pain syndrome during the day and while defecation began to decrease in patients of main group from the 1st day after surgery, whereas it increased and returned to pre-operative level in control group by the 3d day, where remained till the 9th day, only after this it decreased. Significant differences between groups were revealed to 48–49th days. According to profilometry, spasm of internal anal sphincter (IAS) remained in 22/56 patients of main group and in 16/52 patients of control group; on 60th day — in 22/52 (39.3%) and 8/50 (16.0%) patients relatively (p = 0.004). In group of BTA there were statistically significantly fewer days of disability than in group of combination BTA with EF — 7 (6; 15) vs. 20 (15; 30) days. Method of treatment BTA + EF became significant factor, increasing chances of no epithelization on the 30th (odds ratio (OR) = 22.8; 95% CI: 2.93–178.0; р = 0.003) and 45th (OR = 19.5; 95% CI: 5.43–69.8; р < 0.0001) days. On the 60th day presence of IAS spasm was statistically significantly associated with non-healing (OR = 2.68; 95% CI: 1.08–6.66; р = 0.034). The factors which could influence the existence of transitory anal incontinence, were not detected.

CONCLUSION: refusal from EF while BTA's use at a dosage of 80 units allows to achieve defect epithelization on early post-operative period, lower intensity of pain syndrome and significantly decrease time of temporary disability.

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