scholarly journals Kānuka honey for the treatment of herpes simplex labialis within an novel community pharmacy-based network

2021 ◽  
Author(s):  
◽  
Alexander Semprini
Keyword(s):  
Herpes Simplex ◽  
Community Pharmacy ◽  
Primary Outcome ◽  
Healing Time ◽  
Outcome Data ◽  
Acute Episode ◽  
Research Network ◽  
Phase Iii ◽  
Outcome Variable ◽  
Efficacy And Safety

<p>BACKGROUND   Herpes simplex virus infection is common with an estimated global prevalence of over 90%. Of those harbouring the dormant virus, around one third suffer from recurrent episodic reactivation on the vermillion border of the lip, leading to herpes simplex la- bialis (HSL), or a ‘cold sore’. The painful lesions associated with HSL are treated with a range of therapeutic approaches globally, from pharmaceuticals to complementary and alternative medicines (CAM), many of which have a limited or absent evidence base for efficacy and safety. Honey is one such CAM product with growing evidence for efficacy in wound healing, often applied topically for various dermatological ailments and of interest in the management of HSL.   Obtaining robust evidence of the efficacy and safety of novel therapies for HSL is a complex and costly undertaking, traditionally requiring large randomised controlled trials (RCT), and as such has been limited to pharmaceutical funded drug development programmes. Given the paucity of high-quality evidence for many CAM therapies there is a clear need for a novel research methodology to overcome the existing barriers and ensure the timely recruitment of participants with an acute episode of HSL and the collection of valid, standardised outcome data at a modest cost.   RESEARCH AIMS   The primary aim was to investigate the effectiveness, safety and tolerability of a kānuka honey/glycerin cream compared to 5% aciclovir cream in the treatment of HSL. The secondary aim was to establish whether it was feasible to conduct an adequately powered, interventional RCT which includes electronic capture and transmission of data within a New Zealand wide network of community pharmacies, the Pharmacy Research Network (PRN).   METHODS   A phase III, open label, RCT of adults aged 16 and over presenting to a community pharmacy with an acute episode of HSL was conducted between September 2015 and December 2017. Participants were recruited within 72 hours of the onset of symptoms, and randomly allocated to either the kānuka honey/glycerin formulation or 5% aciclovir cream, to be applied five times daily until skin returned to normal or study day 14, whichever occurred first. All outcome data were collected remotely using a customised digital system. The primary outcome was time taken for skin to return to nor- mal at the site of the HSL lesion, analysed by Kaplan-Meier estimates with 95% Confidence Internal (CI). The PRN was established for the purpose of undertaking this trial.   FINDINGS   952 participants with HSL presenting to one of the 76 pharmacies within the PRN were randomised. For the primary outcome variable of time for skin to return to normal, there was no significant difference between kānuka honey/glycerin and 5% aciclovir cream, 9 (95% CI 8 to 9) vs 8 (95% CI 8 to 9) days respectively, Hazard Ratio (HR) (95% CI) 1.06 (0.92 to 1.22) P=0.56. There was no difference between treatments for all secondary outcomes, including healing time to ulceration, healing time from ulceration to resolution, time to resolution of pain, maximal pain, acceptability and adverse events.  The PRN was shown to be a robust clinical research infrastructure, able to fully recruit a large-scale randomised trial at fractional cost of traditional models with acceptable recruitment, attrition and deviation rates.   CONCLUSION   In one of the largest RCTs of a therapy in HSL, there was no evidence of superior effectiveness for either kānuka honey/glycerin or 5% aciclovir cream. This unique, real- world PRN using electronic capture and transmission of data provides a model for future research of CAM in the community setting.</p>

scholarly journals Kānuka honey for the treatment of herpes simplex labialis within an novel community pharmacy-based network

2021 ◽  
Author(s):  
◽  
Alexander Semprini
Keyword(s):  
Herpes Simplex ◽  
Community Pharmacy ◽  
Primary Outcome ◽  
Healing Time ◽  
Outcome Data ◽  
Acute Episode ◽  
Research Network ◽  
Phase Iii ◽  
Outcome Variable ◽  
Efficacy And Safety

<p>BACKGROUND   Herpes simplex virus infection is common with an estimated global prevalence of over 90%. Of those harbouring the dormant virus, around one third suffer from recurrent episodic reactivation on the vermillion border of the lip, leading to herpes simplex la- bialis (HSL), or a ‘cold sore’. The painful lesions associated with HSL are treated with a range of therapeutic approaches globally, from pharmaceuticals to complementary and alternative medicines (CAM), many of which have a limited or absent evidence base for efficacy and safety. Honey is one such CAM product with growing evidence for efficacy in wound healing, often applied topically for various dermatological ailments and of interest in the management of HSL.   Obtaining robust evidence of the efficacy and safety of novel therapies for HSL is a complex and costly undertaking, traditionally requiring large randomised controlled trials (RCT), and as such has been limited to pharmaceutical funded drug development programmes. Given the paucity of high-quality evidence for many CAM therapies there is a clear need for a novel research methodology to overcome the existing barriers and ensure the timely recruitment of participants with an acute episode of HSL and the collection of valid, standardised outcome data at a modest cost.   RESEARCH AIMS   The primary aim was to investigate the effectiveness, safety and tolerability of a kānuka honey/glycerin cream compared to 5% aciclovir cream in the treatment of HSL. The secondary aim was to establish whether it was feasible to conduct an adequately powered, interventional RCT which includes electronic capture and transmission of data within a New Zealand wide network of community pharmacies, the Pharmacy Research Network (PRN).   METHODS   A phase III, open label, RCT of adults aged 16 and over presenting to a community pharmacy with an acute episode of HSL was conducted between September 2015 and December 2017. Participants were recruited within 72 hours of the onset of symptoms, and randomly allocated to either the kānuka honey/glycerin formulation or 5% aciclovir cream, to be applied five times daily until skin returned to normal or study day 14, whichever occurred first. All outcome data were collected remotely using a customised digital system. The primary outcome was time taken for skin to return to nor- mal at the site of the HSL lesion, analysed by Kaplan-Meier estimates with 95% Confidence Internal (CI). The PRN was established for the purpose of undertaking this trial.   FINDINGS   952 participants with HSL presenting to one of the 76 pharmacies within the PRN were randomised. For the primary outcome variable of time for skin to return to normal, there was no significant difference between kānuka honey/glycerin and 5% aciclovir cream, 9 (95% CI 8 to 9) vs 8 (95% CI 8 to 9) days respectively, Hazard Ratio (HR) (95% CI) 1.06 (0.92 to 1.22) P=0.56. There was no difference between treatments for all secondary outcomes, including healing time to ulceration, healing time from ulceration to resolution, time to resolution of pain, maximal pain, acceptability and adverse events.  The PRN was shown to be a robust clinical research infrastructure, able to fully recruit a large-scale randomised trial at fractional cost of traditional models with acceptable recruitment, attrition and deviation rates.   CONCLUSION   In one of the largest RCTs of a therapy in HSL, there was no evidence of superior effectiveness for either kānuka honey/glycerin or 5% aciclovir cream. This unique, real- world PRN using electronic capture and transmission of data provides a model for future research of CAM in the community setting.</p>

scholarly journals Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e017766 ◽  
Author(s):  
Alex Semprini ◽  
Joseph Singer ◽  
Nicholas Shortt ◽  
Irene Braithwaite ◽  
Richard Beasley
Keyword(s):  
New Zealand ◽  
Herpes Simplex ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Healing Time ◽  
Research Network ◽  
Cold Sore ◽  
Cold Sores ◽  
Randomised Controlled ◽  
Medical Grade

IntroductionWorldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as ‘cold sores’, which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban).Methods and analysisThis open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution.Ethics and disseminationNew Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants.Trial registration numberAustralia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results.SCOTT Registration: 15/SCOTT/14Protocol version4.0 (12 June 2017)

Phase III Evaluation of Once-Daily, Oral Therapy with ICL670 (Exjade®) Versus Deferoxamine in Patients with β-Thalassemia and Transfusional Hemosiderosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3619-3619 ◽  
Author(s):  
Maria Cappellini ◽  
Mohamed Bejaoui ◽  
Silverio Perrotta ◽  
Leyla Agaoglu ◽  
Antonios Kattamis ◽  
...  
Keyword(s):  
Quantum Interference ◽  
Safety Data ◽  
Study Drug ◽  
Dry Weight ◽  
Phase Iii ◽  
Outcome Variable ◽  
Efficacy And Safety ◽  
Open Label ◽  
Liver Iron ◽  
Once Daily

Abstract ICL670 (deferasirox) is an investigational once-daily oral iron chelator that has demonstrated the ability to induce sustained, clinically relevant reductions in liver iron content (LIC) in heavily transfused patients with β-thalassemia and iron overload. The efficacy and safety of ICL670 is being assessed in a multicenter, randomized, open-label Phase III study in comparison with deferoxamine (DFO) in patients aged ≥2 years with β-thalassemia and transfusional hemosiderosis. Between March and November 2003, 587 patients began treatment (296 on ICL670; 291 on DFO) in the following 12 countries : Italy (200), Turkey (87), Tunisia (68), US (48), Greece (46), Germany (27), Argentina (24), Belgium (24), Brazil (20), UK (18), Canada (13) and France (12). Based on LIC at baseline (2–3, >3–7, >7–14 and >14 mg Fe/g dw), patients were randomized in a 1:1 ratio to receive either oral ICL670 once daily at doses of 5, 10, 20 or 30 mg/kg, respectively, or subcutaneous DFO at doses of 20–60 mg/kg/day for 5 days/week. Treatment was for one year initially, to be followed by an extension phase during which patients randomized to DFO may switch to ICL670. LIC, the primary outcome variable, was assessed at baseline by liver biopsy or, in some children, non-invasively by magnetic susceptometry using a Superconducting QUantum Interference Device (SQUID). LIC will be reassessed after 12 months of therapy in each patient using the same methodology as at baseline. Liver biopsies are analyzed at a single center (Rennes, France) and SQUID assessments are performed in 3 centers (Turin, Italy; Hamburg, Germany; Oakland, US). At baseline, median (25–75th percentiles) LIC was 13.0 mg Fe/g dw (7.2–21.0) by biopsy and 5.6 (4.0–7.7) in those patients assessed by SQUID. Total body iron balance will be assessed to determine the relative chelation efficacies of ICL670 and DFO. A summary of patient demographics and baseline characteristics (median values or no. of pts) is given in the table. ICL670 has been well tolerated with mild, transient gastrointestinal complaints as the main AEs with a suspected relationship to study drug. As of May 2004, 8 patients on ICL670 and 2 on DFO had discontinued therapy due to AEs. The key efficacy and safety data from the initial 12 months of therapy for all randomized patients will be available late November 2004. Treatment group (by initial dose) ICL670 (n=296) Deferoxamine (n=291) 10 mg/kg n = ≤ 94 20 mg/kg n = 83 30 mg/kg n = 119 <35 mg/kg n = 51 35-<50 mg/kg n = 119 ≥ 50 mg/kg n = 121 Age (yrs) median 15 15 15 15 14 17 No. of pts 2 - <16 years 49 44 60 26 63 56 No. of ≥ pts 16 yrs 45 39 59 25 56 65 No. of males/females 44/50 41/42 54/65 32/19 50/69 61/60 LIC (mg Fe/g dry weight) 4.7 10.6 21.8 4.5 9.1 19.5 No. of pts with biopsy/SQUID* 60/34 69/14 117/0* 36/15 93/26 119/2 Serum ferritin (ng/ml) 1881 1954 3250 1546 2037 2383

Efficacy and Safety of the Gardos Channel Inhibitor, ICA-17043, in Patients with Sickle Cell Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 103-103
Author(s):  
Kenneth I. Ataga ◽  
Laura M. DeCastro ◽  
Paul Swerdlow ◽  
Yogen Saunthararajah ◽  
Wally Smith ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Low Dose ◽  
Phase Iii ◽  
Outcome Variable ◽  
Hydration Status ◽  
High Dose ◽  
Efficacy And Safety ◽  
Range Finding ◽  
Gardos Channel

Abstract The rate and extent of hemoglobin S (HbS) polymer formation in the circulating sickle erythrocyte (RBC) is strongly influenced by the intracellular concentration of HbS. ICA-17043 (bis(4-fluorophenyl)phenyl acetamide) is a novel Gardos channel inhibitor that specifically blocks Ca++-dependent K+ efflux from the human RBC. By limiting the loss of K+, Cl−, and water, this drug preserves the hydration status of the RBC, prevents increases in HbS concentration and thereby inhibits HbS-polymerization. We hypothesized that ICA-17043 could decrease both the hemolytic rate and vaso-occlusive complications of sickle cell anemia (SCA). In a recently completed multicenter, parallel-group, randomized, double-blind, dose-range-finding study, we examined the efficacy and safety of ICA-17043 in patients with SCA. In this 12-week study, 90 patients were randomized into 3 arms: placebo; low dose ICA-17043 (6 mg); and high dose ICA-17043 (10 mg). The primary outcome variable was the change in hemoglobin (Hb) from baseline to the end of the study. A total of 90 subjects were enrolled in this study, 80 of whom completed the 12-week treatment period. Using an intent-to-treat analysis, we found a significant increase from baseline of the total Hb when the subjects in the high dose arm (0.68 ± 0.11 g/dL, S.E.) were compared to those in the placebo arm (0.01 ± 0.12 g/dL), p &lt; 0.001. Although an increase in Hb was also seen in the subjects in the low dose arm (0.28 ± 0.15 g/dL), this smaller change failed to reach statistical significance. Figure Figure In addition to the increase in Hb (as well as similar increases in hematocrit and RBC count), statistically significant decreases were noted after 12 weeks on 10 mg of ICA-17043 vs. placebo in the following variables: a) dense RBC (% with Hb &gt;41 g/dL) [−2.41 vs. −0.08, p &lt; 0.001]; b) reticulocyte count (%) [−4.12 vs. −0.46, p &lt;0.001]; c) LDH (u/L) [−121 vs. −15, p = 0.002]; and d) indirect bilirubin (mg/dL) [−1.18 vs. 0.12, p &lt; 0.001]. ICA-17043 was well tolerated by the subjects. The most common adverse experiences were diarrhea and nausea, both of which occurred more frequently in the subjects receiving active treatment than in those on placebo. No patients died during the study, and only 3 of the 10 patients who dropped out of the study did so because of adverse events. In summary, we found that 12 weeks of treatment with ICA-17043 at a dose of 10 mg/d produced a significant increase in Hb and significant decreases in the various markers of RBC destruction. Furthermore, we found this drug to be safe and well tolerated. Therefore, based on the beneficial, dose-dependent RBC effects, a Phase III study has now been designed that will examine the clinical effect of ICA-17043 on the frequency of vaso-occlusive events in patients with sickle cell disease.

scholarly journals Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: a randomised controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e026201 ◽  
Author(s):  
Alex Semprini ◽  
Joseph Singer ◽  
Irene Braithwaite ◽  
Nick Shortt ◽  
Darmiga Thayabaran ◽  
...  
Keyword(s):  
New Zealand ◽  
Herpes Simplex ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Normal Skin ◽  
Secondary Outcome ◽  
Outcome Variable ◽  
Stage 4 ◽  
Randomised Controlled ◽  
Medical Grade

ObjectiveTo compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis.DesignProspective parallel randomised controlled open-label superiority trial.Setting76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017.Participants952 adults randomised within the first 72 hours of a herpes simplex labialis episode.InterventionsRandom assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily.Outcome measuresThe primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability.ResultsPrimary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported.ConclusionThere was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis.Trial registration numberACTRN12615000648527;Post-results

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