TABLE 1.
Existing studies evaluating mechanisms of action of HOCl
| MECHANSISM OF ACTION | STUDY | METHODS | STUDY OUTCOMES/CLINICAL USE |
|---|---|---|---|
| ANTIMICROBIAL EFFECTS | Reduction of S. aureus in AD skin lesions;9 HOCl solution evaluated using spray application | HOCl vs. water BID for 1 week; N=20 pediatric subjects; evaluations at 3mins and 7 days | Marked reduction in S. aureus colony counts in HOCl group; no change with water; superior clinical improvement in HOCl group in AD grading (P<0.01) |
| In-vivo evaluation of bacterial reductions of S. aureus on healthy forearm skin (n=6); in vitro time-kill study vs. different bacterial and fungal isolates;6 HOCl gel formulation evaluated | Colony counts/log reductions in growth assessed postincubation; rechallenge on 3 other subjects at later date; total of 60 sites tested in vivo; in-vitro time-kill testing completed on 23 bacterial and fungal isolates at timepoints up to 5mins | 99.9% bacterial reduction was shown in in-vitro study inclusive of multiple bacteria (e.g., S. aureus [MRSA], S. pyogenes, Klebsiella spp, P. aeruginosa, Enterobacter spp, Proteus mirablis, C. difficile spores, others) and Candida albicans | |
| Inactivation of S. aureus, E. coli, and Salmonella spp in vitro;3 HOCl solution evaluated | HOCl vs. sodium hypochlorite vs. water in chamber suspensions with fixed bacteria colony counts | Bactericidal effect markedly greater with HOCl vs. comparators (P<0.05); bacteria reduction did not correlate with available chloride concentration | |
| Evaluation of different HOCl solutions in inactivating viability of P. aeruginosa biofilms; included quantitative and ultrastructural evaluation4 | Three formulations of neutral-pH HOCl solution tested (varying free chlorine concentrations) | Established HOCl fomulations that effectively caused biofilm disaggregation and >3-log reduction within 30mins | |
| Evaluation of stabilized/pH-netrual HOCl solution vs. bacteria resistant to domestic bleach/sodium hypochlorite;5 comparisons completed vs. nonstabilized HOCl solution and domestic bleach | Cell suspensions of fixed colony counts of 10 resistant isolates tested after timed exposures to test products; bacterial reduction compared at multiple timepoints; primary comparison at 2mins | Bacterial reductions with stablized/pH-neutral HOCl greater and more consistent than comparators; stabilization/pH neutrality shown to increase antimicrobial activity of HOCl; activity of HOCl confirmed vs. resistant bacterial strains | |
| Bacterial susceptibility, time-kill testing (S. aureus, P. aeruginosa, C. albicans);1 HOCl solution evaluated | MBC testing; time-kill study evaluating time of complete growth absence; biofilm eradication assessed in growth wells | Rapid time-kill of organisms with MBC range of 1/32–1/64; biofilm magnitude and organism content within biofilms were decreased; dose-dependent response in a species-specific manner | |
| Antiviral activity in vitro including enveloped and nonenveloped virus types;7 assessed poliovirus-1, rhinovirus-1, respiratory syncytial virus, HSV-1, HSV-2, influenza A H1 and H3, West Nile virus, and Norwalk virus surrogate; HOCl solution evaluated | Target cells infected with HOCl-treated or saline-treated (control) virus exposed for 1min and 5mins; cells in 48-well culture plates infected with either treated virus, incubated, and evaluated for cytopathic changes at 24–48hrs | Collectively, HOCl-exposed enveloped and nonenveloped viruses decreased by a log10 factor ≥5 with exposure of at least 1min; complete virus inactivation occurred within 5 mins | |
| INFLAMMATORY SKIN DISORDERS/PRURITUS | HOCl gel in mild-to-moderate seborrheic dermatitis (n=25) affecting face and/or scalp;12 open study; monotherapy; gel vehicle with dimethicone 2% | Application BID for 28 days; evaluations included IGA, SGA, pruritus, burning, and stinging | Endpoint success by IGA was 33% at Day 14 and 52% at Day 28; SGA of efficacy/improvement compared with baseline was 62% at Day 28; patients demonstrated improvements in pruritus and decrease in scaling |
| HOCl gel evaluated for treatment of pruritus associated with AD (n=29)13 | Investigator-blinded, randomized 72-hr study; included 19 treated with HOCl BID/PRN and 10 untreated (control); pruritus score of ≥2 on a 4-point scale (AD patients); evaluations included IGA, PGA, and VAS; IGA evaluation included erythema, lichenification, desquamation, and excoriation, and PGA included peeling, stinging, itching, and burning; VAS itch score was linear placement to assess severity (0mm=none, 154mm=most itching) | Mean changes from baseline noted in IGA and PGA were greater in the HOCl arm vs. untreated (control) (P=0.012 and P=0.128); mean % change in VAS itch score was improved significantly in HOCl group (-34.78) compared with untreated (control) group (+24.56) (P=0.007); 73.7% of HOCl group and 30.0% of untreated group noted a reduction in pruritus from baseline to 72hrs. | |
| HOCl solution evaluated for treatment of facial acne vulgaris (n=87);18 HOCl solution (n=39) vs. BP (n=24) vs. placebo (n=24) | Double-blind, randomized, placebo-controlled, 12-week study; both actives and placebo applied BID to face; inclusion: 10–50 inflammatory papules/pustules (mean range: 33.5–35.3); no nodules; age range was 15–22 years; 46 women/41 men | Clinical improvements (excellent, good) comparable between HOCl and BP (23% vs. 21% and 54% vs. 50%, respectively); both HOCl and BP were markedly superior to placebo; there was no need for dosage adjustments in any groups and there were no local AEs. | |
| DIABETIC FOOT ULCERS/ POSTSURGICAL WOUNDS/ SCARS | Open-label study of presurgical response to HOCl solution (n=110) vs. PI solution (n=108) in infected diabetic foot wounds/ulcers; evaluated as part of comprehensive wound care regimen15 | Alternative assignment to be treated with HOCl or PI + daily dressing changes; baseline and postsurgical colony counts, healing time, and skin reactions noted; baseline number of bacteria similar in both groups | Significantly greater bacterial clearance in HOCl group (P<0.001); significantly shorter median healing time in HOCl group (43 days) vs. PI group (55 days) (P<0.0001); no adverse skin reactions in HOCl group (0/110) vs. 18 in PI group (18/108) |
| Postsurgical therapy of infected diabetic foot ulcers healing by second intention (n=40);14 HOCl solution evaluated vs. PI + systemic antibiotic therapy and surgical debridement; exclusions included renal failure and immunosuppression | Patients were followed up weekly over 6mos; evaluation of healing rate, time to negative cultures, duration of antibiotic therapy, number of reinterventions, and AEs were completed | Superior healing rates at 6mos in HOCl group (90% vs. 55%); p<0.01) were noted; significantly shorter time to negative culture and duration of antibiotic use in HOCl group (P<0.05); reinterventions significantly more in number (P<0.05) and reinfection more frequent (P<0.01) in PI group (9 cases vs. 1 case); no difference was seen in AE rates; both low/safe | |
| Evaluation of HOCl/silicone gel vs. a branded silicone gel for hypertrophic scars and keloids (n=40);25 study not powered for statistical superiority between products (trend analysis possible) | Double-blind, randomized study with TID application of study gel for 8wks (56 days); qualified scars were widespread hypertrophic scars and keloids present for 3–12mos; evaluations at Days 14, 28, 56, 84, and 112 using VSS and symptom scores performed; IGA score and subject satisfaction data at Day 56 (end of therapy) and at Day 112 (end of study) collected | Individual scores for pain and pruritus decreased (improved) in both groups over course of study; mean reduction of scores greater in HOCl/silicone group; IGA assessment ratings at Days 56 and 112 very good/good in 6 and 11 subjects in HOCl/silicone group and in 5 and 5 subjects in silicone group, respectively; trends showed superiority in HOCl/silicone group; no major AEs noted in either group | |
| HOCI: Hypochlorous acid; AD: atopic dermatitis; BID: twice daily; MRSA: methicillin-resistant Staphylococcus aureus; MBC: minimum bactericidal concentration; HSV: herpes simplex virus; IGA: Investigator Global Assessment; SGA: Subject Global Assessment; PGA: Participant Global Assessment; PRN: when necessary; VAS: Visual Analog Scale; BP: benzoyl peroxide; PI: povidone iodine; TID: 3 times daily; AE: adverse event; VSS: Vancouver Scar Scale | |||