title: Recombinant streptokinase vs hydrocortisone suppositories in acute hemorrhoids: A randomized controlled trial.
abstract: OBJECTIVE
  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 5(th)-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 3(rd) 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 10(th) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Bernal
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Georgina
authors.initials: G
authors.lastname: Castellanos-Sierra
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Valenzuela-Silva
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Karem M
authors.initials: KM
authors.lastname: Catasús-Álvarez
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Osmany
authors.initials: O
authors.lastname: Martínez-Serrano
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Odalys C
authors.initials: OC
authors.lastname: Lazo-Diago
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Cimara H
authors.initials: CH
authors.lastname: Bermúdez-Badell
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: José R
authors.initials: JR
authors.lastname: Causa-García
authors.affiliation: Francisco Hernández-Bernal, Carmen M Valenzuela-Silva, Karem M Catasús-Álvarez, Odalys C Lazo-Diago, Cimara H Bermúdez-Badell, Pedro A López-Saura, Clinical Research Direction, Center for Genetic Engineering and Biotechnology, Havana 74110, Cuba.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Domínguez-Suárez
mesh_terms: D000208:Acute Disease; D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003462:Cuba; D004334:Drug Administration Schedule; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006484:Hemorrhoids / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D013300:Streptokinase / Q000008:administration & dosage* / Q000009:adverse effects; D013488:Suppositories; D017131:Thrombectomy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D013488:Suppositories; C021650:hydrocortisone acetate; D013300:Streptokinase; D006854:Hydrocortisone
keywords: Hemorrhoids; Hydrocortisone acetate; Randomized clinical trial; Streptokinase; Suppository; Thrombolysis