Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7305
Peer-review started: November 15, 2014
First decision: December 26, 2014
Revised: January 10, 2015
Accepted: January 21, 2015
Article in press: January 21, 2015
Published online: June 21, 2015
AIM: To compare the efficacy and safety of recombinant streptokinase (rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.
METHODS: A multicenter (11 sites), randomized (1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written, informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h (first 3 units) and afterwards every 12 h until 8 administrations were completed (schedule A), one unit every 8 h until 6 units were completed (schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5, and 10 d post-inclusion. The main end-point was the 5th-day response (disappearance of pain and bleeding, and ≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.
RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170 (91.8%; 95%CI: 87.3-96.2), 155/170 (91.2%; 95%CI: 86.6%-95.7%), and 46/170 (27.1%; 95%CI: 20.1%-34.0%) with rSK (schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9% differences (95%CI: 56.7%-72.2% and 55.7%-72.0%) were highly significant (P < 0.001). This advantage was detected since the early 3rd day evaluation (68.8% and 64.1% vs 7.1% for the rSK and active control groups, respectively; P < 0.001) and was maintained even at the late 10th day assessment (97.1% and 93.5% vs 67.1% for rSK and hydrocortisone acetate, respectively; P < 0.001). Time to response was 3 d (95%CI: 2.9-3.1) for both rSK groups and 10 d (95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant (P < 0.001). All subgroup stratified analyses (with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in 4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively (P < 0.001). There were no adverse events attributable to the experimental treatment.
CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile.
Core tip: Medical treatments for acute hemorrhoidal disease very seldom come from randomized, controlled clinical trials. The paper describes recombinant streptokinase suppositories, a candidate to a new therapeutic alternative based on thrombolysis. The results show a significant efficacy advantage with respect to hydrocortisone acetate, a widely-used, over-the-counter product.