Download Manuka honey vs. hydrogel – a prospective, open label, multicentre

ORIGINAL ARTICLE
Manuka honey vs. hydrogel – a prospective, open label, multicentre,
randomised controlled trial to compare desloughing efficacy and healing
outcomes in venous ulcers
Georgina Gethin and Seamus Cowman
Objective. Comparison of desloughing efficacy after four weeks and healing outcomes after 12 weeks in sloughy venous leg
ulcers treated with Manuka honey (Woundcare 18+) vs. standard hydrogel therapy (IntraSite Gel).
Background. Expert opinion suggests that Manuka honey is effective as a desloughing agent but clinical evidence in the form of
a randomised controlled trial is not available. There is a paucity of research which uses Manuka honey in venous ulcers.
Design. Prospective, multicentre, open label randomised controlled trial.
Method. Randomisation was via remote telephone. One hundred and eight patients with venous leg ulcers having ‡50% wound
area covered in slough, not taking antibiotics or immunosuppressant therapy were recruited from vascular centres, acute and
community care hospitals and leg ulcer clinics. The efficacy of WoundCare 18+ to deslough the wounds after four weeks and its
impact on healing after 12 weeks when compared with IntraSite Gel control was determined. Treatment was applied weekly for
four weeks and follow-up was made at week 12.
Results. At week 4, mean % reduction in slough was 67% WoundCare 18+ vs. 52Æ9% IntraSite Gel (p = 0Æ054). Mean wound
area covered in slough reduced to 29% and 43%, respectively (p = 0Æ065). Median reduction in wound size was 34% vs. 13%
(p = 0Æ001). At 12 weeks, 44% vs. 33% healed (p = 0Æ037). Wounds having >50% reduction in slough had greater probability
of healing at week 12 (95% confidence interval 1Æ12, 9Æ7; risk ratio 3Æ3; p = 0Æ029). Infection developed in 6 of the WoundCare
18+ group vs. 12 in the IntraSite Gel group.
Conclusion. The WoundCare 18+ group had increased incidence of healing, effective desloughing and a lower incidence of
infection than the control. Manuka honey has therapeutic value and further research is required to examine its use in other
wound aetiologies.
Relevance to clinical practice. This study confirms that Manuka honey may be considered by clinicians for use in sloughy venous
ulcers. Additionally, effective desloughing significantly improves healing outcomes.
Key words: nursing, randomised control trials, research, tissue viability, venous leg ulcer, wound care
Accepted for publication: 11 June 2008
Introduction
The premise that wound healing is impaired in the presence
of devitalised tissue is well supported within the literature
(Sieggreen & Malkebust 1997, Baharestani 1999, NICE
Authors: Georgina Gethin, PhD, RGN, Dip HE wound care, Dip
Anatomy, Dip Applied Physiology, Faculty of Nursing and
Midwifery, Royal College of Surgeons in Ireland, Dublin, Ireland;
Seamus Cowman, MSc, PhD, RNT, RGN, RPN, FFNMRCSI, PG
Cert (Adults), Dip N (London), Faculty of Nursing and Midwifery,
Royal College of Surgeons in Ireland, Dublin, Ireland
2001). Its removal, when consistent with treatment goals, is
considered the first step in wound bed preparation of the
chronic wound (Falanga 2002). Debridement methods range
from surgical to natural autolytic debridement and the
method is dependent on the condition of the wound bed,
Correspondence: Georgina Gethin, Lecturer, Research Centre,
Faculty of Nursing and Midwifery, Royal College of Surgeons in
Ireland, 123 St Stephens Green, Dublin 2, Ireland. Telephone: 00 353
1 4022202.
E-mail: [email protected]
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
doi: 10.1111/j.1365-2702.2008.02558.x
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G Gethin and S Cowman
resources, knowledge and patient and clinician treatment
goals.
Venous leg ulcers (VLU) continue to affect up to 2% of
the population (Nelzen et al. 1996, O’Brien et al. 2000,
Moffatt et al. 2004). While compression remains the
primary treatment option for uncomplicated VLU the
plateau in healing rates of 32–50% after 12 weeks of
compression and recurrence of 50% within three months of
healing (Monk & Sarkany 1982, Thomson et al. 1996,
Moffatt et al. 2004) warrants investigation into which
ulcers are healing and the characteristics of those that do
not. Systematic reviews of dressings used in the management of VLU have failed to demonstrate improved healing
outcomes above that expected with compression alone
(Bradley et al. 1999, Palfreyman et al. 2006). Arguably,
failure to stratify healing outcomes based on the condition
of the wound bed at baseline may account for this.
Essentially one would not expect a sloughy, large, heavily
colonised VLU to have the same rate of healing as a clean
granulating ulcer.
While the use of honey in wound management dates back
2000 years (Forrest 1982, Molan 2006), evidence of efficacy
in modern literature is predominantly in the acute wound
domain. A specific type of honey, namely Manuka honey
(MH) from the Leptospermum scoparium bush found
throughout New Zealand and Australia, is gaining recognition as a wound management agent (Cooper 2001, Gethin &
Cowman 2005, Molan 2006). However, claims of MH as a
desloughing agent are based on in vitro research and case
studies and have not been tested heretofore in a rigorous
clinical study. The desloughing capacity of MH may permit it
to work synergistically with compression therapy to treat
VLU and improve outcomes.
2000) determined that 156 subjects randomly allocated
to two equal groups of 78 were required. The power of
the study was based on an 80% power to detect a
minimum difference of 20% at the 5% two-sided significance level.
Selection and description of participants
Adults presenting with VLU having ‡50% wound area
covered in slough and able to provide written informed
consent were considered for inclusion. Inclusion and exclusion criteria are listed in Table 1 and were based on Ankle
Brachial Pressure Index (ABPI) of ‡0Æ8 where no other
causative aetiology was present and the ulcer appeared to be
venous on clinical examination. Baseline data collection
included patient gender, age, wound size and duration, ulcer
location and history of recurrence. Medical information
included history of deep venous thrombosis (DVT), hypertension, trauma or surgery to the affected limb, diabetes,
immunosuppression and current medications. The uppermost ulcer or the largest ulcer was selected if more than one
was present, providing this ulcer met the inclusion criteria.
Each participant could only contribute one ulcer to the
study.
Randomisation
Following screening and when consent was provided, patients
were randomised via remote phone allocation to either
treatment group. The allocation sequence was generated
Table 1 Inclusion and exclusion criteria
Study outcomes
The primary outcomes were determination of the ability of
MH to deslough VLU over four weeks and measurement of
its effects on healing rates after 12 weeks when compared
with a standard agent.
Methods
Study design
This prospective, open label, 12-week, multicentre, randomised controlled clinical trial (RCT) was conducted
between February 2003–January 2006. Ethical approval
from each area was obtained. The formula for comparison
of proportions in two independent groups (Daly & Bourke
2
Inclusion criteria
Having a venous ulcer
Being over 18 years of age
Able to provide written informed consent
Having ‡50% of wound bed covered in slough
Ulcer size < 100 cm2
Exclusion criteria
Less than 18 years
Unable to provide written informed consent
Having an ulcer > 100 cm2
Ulcer diagnosed as being malignant
Having a cavity wound
Clinical diagnosis of wound infection
Currently taking antibiotics for any reason
Currently taking oral immunosuppressant
Having poorly controlled diabetes
Having previously enrolled into the study
Pregnant women or lactating mothers
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
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using serially numbered, sealed, opaque envelopes, prior to
the study by two persons independent of the study.
Treatments
All wounds were cleansed with warm tap water at each visit
prior to assessment and treatment. MH dressing (Woundcare
18+; Comvita, Te Puke, New Zealand), a viscous orange/
brown topical agent, at a dosage of 5 g/20 cm2 was applied
weekly. The control group had hydrogel therapy (HT;
IntraSite Gel; Smith & Nephew, Hull, UK) at a dosage of
3 g/20 cm2 applied weekly. The viscosity of the agents
accounted for the dose differential. HT was selected as this
represented the routine practice for sloughy wounds. Secondary dressings were standardised as Allevyn hydrocellular foam
(Smith & Nephew). Compression therapy was continued in all
cases, the most common form being four-layer bandages. The
treatment period was four weeks. After this time, all patients
received follow-on treatment based on clinical assessment
of the wound by the local investigator, which varied from
patient to patient. Follow-up was conducted at week 12.
Wound assessment
All wound assessments were completed at baseline and at
weekly intervals for four weeks by the local clinical investigator who had received training in leg ulcer management. A
determination of healed or not healed was made at week 12.
Weekly wound measurements were conducted using Visitrak
digital planimetry (Smith & Nephew); the percentage of the
wound bed covered in slough was assessed quantitatively. A
pretrial inter-rater reliability (IRR) study determined the level
of agreement among three raters when assessing slough as a
percentage within the wound bed. The inter-class correlation
for slough was 0Æ95 (95% confidence interval, CI 0Æ88–0Æ98,
p < 0Æ001). The presence or absence of other tissues,
including granulation, epithelial and necrotic, was recorded
at each assessment. Blinded outcome assessment was not
possible because of obvious differences in the colour and
presentation of the products, specifically orange staining of
the peri-wound skin when MH was used.
An open label, multicentre, prospective study
Statistical analysis
All statistical analyses were performed using SPSS version 14
and Stata release 9Æ2 by a statistician blinded to the treatment
allocations on the intention-to-treat population. All patients
were included in the final analysis. All tests were conducted at
the two-sided a = 0Æ05 level of significance. Regression was
used to model the effects of treatment on wound size.
Ordered logistic regression was used to model the effects of
treatment on slough as this variable departed markedly from
the normal distribution and exhibited clustering of values.
Binomial regression was used to model binary outcomes
which allowed the treatment effect to be expressed as a risk
ratio (RR). Slough was calculated as the percentage of the
wound bed that it covered at the time of assessment. The
difference from baseline to end of week 4 assessment was
calculated as: [original percentage of wound area covered in
slough – final percentage of wound area covered in slough].
Wound area was re-expressed as wound diameter and
changes were calculated as: [original wound diameter – final
wound diameter]. The chi-square test was used to compare
categorical demographic and baseline variable response
profiles. Independent t-test analysed baseline demographic
and wound variables. Wilcoxon-signed rank test analysed
median differences in wound size. In addition to treatment
effects, subset analyses were performed comparing the
Margolis scores (Margolis et al. 2000) of each group at
baseline and determination of outcomes at week 12 of all
wounds based on this score.
Results
Demographic and baseline values
The flow of participants through the trial is presented in
Fig. 1. One hundred and eight patients were enrolled from 10
sites, including acute and community hospitals, vascular and
leg ulcer clinics over 34 months. There were no statistical
baseline differences between groups (Table 2). Complete
screening data was only available from one large centre. The
reasons for non-inclusion from this centre are presented in
Table 3.
Specific withdrawal criteria
Patients who commenced antibiotic or immunosuppressant
therapy for any reason during the treatment period were
withdrawn. The rationale being, that any improvement in the
wound in the four weeks could not be confidentially
attributed to the topical agent and may have been because
of antibiotics or steroid treatment.
Reduction in slough
After four weeks, 80% (n = 86) of all wounds had a
reduction of >50% slough. There was no statistically
significant difference at week 4 between treatments (95%
CI – 0Æ370, 1Æ00; p = 0Æ367; Table 4). It is noteworthy that a
slough reduction of at least 50% by week 4 was associated
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
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G Gethin and S Cowman
Assessed for eligibility n = 256 *
Excluded n = 148
Reason for exclusion:
Did not meet criteria n = 142
Refused to participate n = 6
See Table 2
Randomised n = 108
Manuka-honey group (a)
n = 54
Hydrogel group (b)
n = 54
Received allocated treatment n = 54
Did not receive n = 0
Received allocated treatment n = 54
Did not receive n = 0
Lost to follow up n = 0
Withdrawal
n=9
Lost to follow up n = 0
Withdrawal
n = 17
Reason for withdrawal:
Infection in study wound
n=6
Infection elsewhere
n=1
Patient request
n=1
Non-compliance with treatment n = 1
Reason for withdrawal:
Infection in study wound
n = 12
Infection elsewhere
n=1
Patient request
n=4
Non-compliance with treatment n = 0
Analysed
Analysed
n = 54
n = 54
*complete screening data from one centre only. Numbers randomised are from all
centres
with a higher probability of healing at 12 weeks across all
groups (95% CI 1Æ12–9Æ7; RR 3Æ3, p = 0Æ029).
Healing outcomes
Epithelisation was visible at an earlier stage in the MH group
and this difference was statistically significant (v2 = 9Æ906;
p = 0Æ042). Healing outcomes are presented in Table 4. The
median wound size at baseline for all wounds was 4Æ7 cm2
and this reduced by 23% to 3Æ65 cm2 at week 4. The MH
group had a 34% reduction in median size vs. 13% in the HT
group; this difference was statistically significant (z = –4Æ609;
p < 0Æ001). The mean reduction in wound size in all wounds
after four weeks was 65Æ9% (SD 23Æ3) in those that healed at
12 weeks vs. 19% (SD 23Æ2; p < 0Æ001) in those that did not
heal.
4
Figure 1 Flow of participants through
the trial.
The Margolis index (Margolis et al. 2000), while intended
as a potential predictor to healing at 24 weeks, was included
here for outcomes at 12 weeks to aid interpretation of the
results. Patients scored 1 for wound duration ‡6 months and
scored 1 if the size was ‡5 cm2. Thus, a higher score indicates
a poorer prognosis for healing at 24 weeks. Sixty nine per
cent of those with a score of zero at baseline healed vs. 21%
of those with a score of 1 vs. 9Æ5% of those with a score of 2.
When adjusted for Margolis score, the healing rate at
12 weeks was significantly higher in the MH group (OR
3Æ1, 95% CI 1Æ15–8Æ35, p = 0Æ025).
Adverse events
There were no adverse events directly attributable to either
wound agent. Exactly 24% (n = 26) withdrew (n = 9 MH,
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
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An open label, multicentre, prospective study
Table 2 Baseline characteristics of participants by treatment group
Characteristics
Age (years)*
Wound duration (weeks)*
Wound size (cm)*
% wound bed covered in
slough
Hypertension
Current smoker
History of deep vein
thrombosis in affected
leg
Ulcer recurrence
Margolis score = 0
Margolis score = 1
Margolis Score = 2
Honey
treatment
(n = 54)
Hydrogel
therapy
(n = 54)
68Æ50 (13Æ50)
39Æ46 (40Æ50)
10Æ52 (12Æ30)*
5Æ4
85Æ5 (21Æ7)
68Æ30
29Æ93
9Æ87
4Æ2
78Æ15
14
10
5
19
8
4
27
18
16
20
31
25
17
12
(15Æ10)
(35Æ20)
(12Æ90)*
(23Æ3)
Values are mean* (SD) or median where specified.
Table 3 Reason for non-randomisation based on screening data from
one centre
Reason for non-randomisation
Number (%)
Clean wound bed
Ankle Brachial Pressure Index < 0Æ8
On antibiotics
Unable to attend for duration of study
Ulcer > 10 · 10 cm2
Patient request
Unable to consent
Infection in study wound
On steroid therapy
Not a venous ulcer
Other
Total
15
47
3
12
6
6
3
8
4
38
6
148
(10)
(31)
(2)
(8)
(4)
(4)
(2)
(5)
(2)
(25)
(4)
n = 17 HT), reasons for which are presented in Table 4. The
low numbers of withdrawals in each group precluded
meaningful statistical analysis. However, analysis of time to
withdrawal because of infection using survival analysis shows
that there is a difference but it is just short of statistical
significance using the log-rank test (p < 0Æ07).
Discussion
There is little knowledge of healing outcomes specific to the
condition of the wound bed in sloughy VLU. This is
important if we are to gain deeper understanding of which
ulcers heal at 12 weeks and advance the knowledge related to
the appropriate use of topical agents in wound management.
This RCT represents the first and largest multicentre, clinical
trial designed to assess the effectiveness of MH for the
treatment of sloughy VLU. A pragmatic study design rather
than an efficacy trial was conducted so that findings may be
applicable to the general patient population and emulate
routine practice.
For the primary outcome, a statistically significant differential efficacy in desloughing between the two treatment
groups could not be shown. However, they are clinically
significant in that a greater percentage of slough was removed
by MH than by the HT. Placing the primary outcome results
in the perspective with other studies is challenging because of
study differences in inclusion criteria and duration of treatment. One can conclude that in the desloughing of VLU, MH
is slower than larval therapy or curettage (Wayman et al.
2000, Williams et al. 2005), but superior to some hydrogels,
enzymatic agents, hydrocolloids, paraffin gauze or cadexomer iodine (Hansson 1998, Wayman et al. 2000, Konig et al.
2005).
These findings advance the knowledge gained from other
research on desloughing agents, as other studies failed to
follow patients for 12 weeks (Flanagan 1995, Fear &
Thomas 1996, Wayman et al. 2000, Konig et al. 2005).
The second observation period of 12 weeks demonstrated the
benefit to healing outcomes when wounds were desloughed.
After 12 weeks, all wounds with a reduction in slough of
‡50% had higher healing rates than those where £50%
slough was removed (RR 3Æ3; p = 0Æ029) supporting the
premise that removal of devitalised tissue promotes wound
healing.
In comparison, one study which followed patients for
20 weeks did not demonstrate superiority of healing rates at
12 weeks compared with those in this RCT (Williams et al.
2005). Williams et al. (2005) reported a healing rate of
14Æ6% (n = 5) at 12 weeks when wounds were debrided
using curettage. A possible explanation for the poorer healing
rates may lie in the fact that the latter debrided wounds as a
one-time event, whereas debridement was continued over
four weeks in the present study. The benefit of on-going or
maintenance debridement on healing rates has been demonstrated previously in the management of diabetic foot ulcers
(Steed et al. 1996) but not in VLU. It is therefore proposed
that a four-week observation period can guide clinicians on
whether to continue with, or change a treatment based on the
reduction in wound size. But, to determine efficacy of an
agent on healing, outcomes should be evaluated over at least
12 weeks.
MH may deslough wounds through a combination of
pathways. First, the honey exerts an osmotic effect within the
wound bed as it draws fluid from the deeper wound tissue to
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
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G Gethin and S Cowman
Table 4 Study outcomes at weeks 4 and 12 based on treatment group
Honey
therapy,
week 4
Characteristic
2
Wound size (cm )*
Wound size (cm2)
Healed, n (%)
% wound bed covered in Slough
% reduction in slough
Withdrawal
Infection in reference wound
Infection elsewhere
Patient request
Non-compliance
Did not attend follow-up
Honey
therapy,
week 12
8Æ25 (11Æ57)
3Æ56
Hydrogel
therapy,
week 4
Hydrogel
therapy,
week 12
8Æ24 (12Æ11)
3Æ66
24 (44)
29 (35)
67 (36Æ41)
18(33)
43 (44)
52Æ6 (45Æ1)
9
6
1
0
1
1
(16Æ6)
(11Æ1)
(1Æ85)
(1Æ85)
(1Æ85)
17 (31Æ48)
12 (22Æ2)
1 (1Æ85)
3 (5Æ5)
0
1 (1Æ85)
p-value (95% CI)
0Æ16 (0Æ1, 0Æ55)
0Æ001
0Æ03 (1Æ02, 1Æ88) RR 1Æ38
0Æ06 ( 29Æ2, 0Æ89)
0Æ05 ( 0Æ28, 31Æ08)
0Æ07
Values are mean* (SD) or median where specified.
CI, confidence interval; RR, risk ratio.
the surface (Chirife et al. 1982). This process aids cleansing
and removal of devitalised tissue (Chirife et al. 1982).
Second, honey maintains a moist wound environment
(Condon 1993, Cooper 2001, Molan 2001), which facilitates
autolysis (Sieggreen & Malkebust 1997, Baharestani 1999,
Ayello & Cuddigan 2004).
In addition to autolysis, MH may also deslough by
lowering wound pH (Gethin et al. 2008). Research has
shown a statistically significant reduction (p < 0Æ001) in pH
of chronic wounds after two weeks of MH use (Gethin et al.
2008). In the latter study, when slough remained in the
wound bed, the pH was elevated at 7Æ7 and the wound size
increased by 6%. Conversely, when slough was removed, the
pH was £7Æ6. A clinically and statistically significant finding
from this study was that a reduction in 0Æ1 pH units
correlated with an 8Æ1% reduction in wound size
(p = 0Æ012; Gethin et al. 2008).
In determining the efficacy of MH to deslough VLU, it was
important from a clinical perspective to ascertain if any
benefit was observed on wound size and healing rates. The
four-week treatment period was guided by clinical experience
and research indicates that a 30% reduction in wound size is
a good predictor of healing (Tallman et al. 1997, Kantor &
Margolis 2000, Margolis et al. 2000, Meyer et al. 2002,
Flanagan 2003, Steed et al. 2006). However, stopping the
trial at this stage would fail to demonstrate effects on healing
outcomes, which, it could be argued, are the only outcomes
of interest to clinicians and patients.
After four weeks, the mean 19% reduction in wound size
could be interpreted as a poor outcome when compared with
the recommended 30% (Flanagan 2003). However, a probable reason for this when compared with other research
(Tallman et al. 1997, Kantor & Margolis 2000, Margolis
6
et al. 2000, Gethin & Cowman 2005), may be related to the
compromised state of the wound bed at the start of the study
wherein slough was the predominant tissue type. It may be
that the recommended 30% reduction is most appropriately
applied to clean granulating wounds and not sloughy VLU.
At the four-week time point, MH outperformed the HT with
a median reduction in wound size superior in the MH-treated
wounds. Wound healing trajectories have demonstrated
significant differences in healing curves of healing vs. nonhealing VLU (Steed et al. 2006). This study is in agreement
with Steed et al. (1996) as ulcers that healed had significantly
greater reduction in wound size at four weeks that those that
did not heal.
This study has used the Margolis score on a specific subset
of VLU, i.e. ‡50% slough and reported outcomes after
12 weeks. The Margolis score represents a step towards a
targeted therapeutic approach to wound management, as it
considers both size and duration. Sixty-nine per cent healing
occurred in wounds with a zero score. This is distinctly
different from the 9Æ5% healed in those with a score of 2.
Wounds treated with MH had statistically superior healing
rates after 12 weeks when size and duration were considered.
One could thus conclude that the expected healing rates of
clean granulating VLU, <5 cm2 and <6 months duration
would be much greater than the 39% healed in this study.
This figure may set a benchmark against which other topical
agents can be compared. Based on the observations made in
this study, it is recommended that future research on the
efficacy of topical agents in the treatment of VLU be stratified
according to the condition of the wound bed together with
the size and duration of the wound. Thus, agents that have
not been able to demonstrate superiority over standard care
to date may be able to report more clinically meaningful and
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
Original article
statistically significant outcomes. The 39% healing rate after
12 weeks compares favourably with the 40–50% reported in
other VLU studies (Duby et al. 1993, Thomson et al. 1996,
Wilkinson et al. 1997, Bale & Harding 2003) but less than
one study in which 55% healing was achieved when
compression and MH dressings were used (Jull et al. 2008).
The current study differs from that of Jull et al. (2008) as the
median wound size in their study was 2Æ7 cm2, exactly half of
that in our study. Additionally, the majority of patients had a
zero Margolis score in the Manuka group in the latter study
while the majority had a score of ‘2’ in this study. This
underscores the differences in expected healing outcomes
based on the condition of the wound at baseline. Furthermore, the mean ulcer duration was 34Æ6 weeks in the present
study, arguing potentially longer healing times than predicted
by other research (Kantor & Margolis 2000).
Further comparison with other studies designed to evaluate
the use of dressings in VLU management is limited as many
studies fail to state the condition of the wound bed at the start
of treatment (Blair et al. 1988, Thomas et al. 1997, Franks
et al. 2007). One RCT was identified which used honey (not
Manuka) in the management of chronic wounds, but this
study excluded VLU (Oluwatosin et al. 2000). Direct
comparison is not applicable to a further study which
compared honey with IntraSite Gel (Ingle et al. 2006). The
latter study excluded wounds of the legs and used a local,
unsterile, unprocessed honey.
Infection was the most common reason for withdrawal at
16Æ6% (n = 18). Although prospective patients with clinical
signs of infection were excluded from the trial, research has
shown that chronic ulcers are persistently colonised subclinically (Trengove et al. 1996, Bowler & Davies 1999). Infection
rates are concerning given that in both groups, 18 patients
failed to complete the four-week treatment period because of
interrupted treatment owing to wound infection. Although, no
statistical differences were noted in the frequency of infection
between the groups, the two study treatments differed in terms
of their antimicrobial properties and this may explain the
differences in infection rates in sloughy wounds.
Strengths and limitations
The prestudy pilot phase identified that when MH was used
orange staining of the peri-wound skin was noted, introducing the possibility of ascertainment bias. However, this was
minimised by the use of percentage tissue type, the IRR of
which had been established, wound measurement and the
multicentre study. A second limitation was failure to enrol
the predetermined number of participants. The duration of
accrual extended to 34 months. Continuation of the trial to
An open label, multicentre, prospective study
enrol 156 participants would have necessitated a further
18 months of recruitment which represented an unrealistic
timeframe for this type of study. This study has several
strengths most notably that it is the largest study of
desloughing in VLU and the only study to have determined
the efficacy of MH to deslough. Furthermore, it establishes
the healing outcomes of VLU based on the condition of the
wound bed. The direct comparison of honey with another
agent provides more clinically meaningful interpretation of
the findings than studies in which standard care or ‘usual
care’, which is not standardised, is used.
Implications for practice
There has been an exponential rise in demand for evidence to
support clinical practice. While the clinician is faced with an
ever-increasing choice of topical agents to manage wounds,
Cochrane reviews have identified that the evidence for many
of these agents is based on methodologically inferior research
studies (Bradley et al. 1999, O’Meara et al. 2001, Palfreyman
et al. 2006). This study has contributed to evidence-based
practice through the conduct of a well-designed RCT which
answered a clinically relevant question. Whether clinicians
use MH in their armoury of products will remain a choice
based on their local protocols for purchase and selection of
products. Nonetheless, this study will allow them to base
their decision on an unbiased assessment of objective
evidence rather than on a subjective compilation of opinion.
Conclusion
When tested in the rigours of an RCT containing the largest
sample size in a study of debridement of VLU, MH-treated
wounds exhibited an increased incidence of healing, more
efficacious desloughing and lower rates of infection as
compared with the controls. MH has a beneficial therapeutic
effect in modern wound management.
Contributions
Study design: GG; data collection: GG; data analysis: RC*,
GG, SC and manuscript preparation: GG, SC.
*RC is Prof. Ronan Conroy, DSc, Associated Professor of
Biostatistics in RCSI conducted the primary data analysis.
Acknowledgement
The authors are indebted to Prof. Ronan Conroy for
statistical analysis and the tissue viability nurses in Sligo
General Hospital.
2008 The Authors. Journal compilation 2008 Blackwell Publishing Ltd, Journal of Clinical Nursing
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G Gethin and S Cowman
Funding
This study was funded by research grant-aid from the
Research and Education Foundation in Sligo General Hospital, European Wound Management Association and the
Health Research Board of Ireland. These funders had no role
in design and conduct of the study, collection, analysis and
interpretation of data or in the preparation of the manuscript,
review or approval of manuscript, in protocol development,
patient recruitment, data collection, data analysis or manuscript preparation. Grant-aid was obtained through an
application, interview and international peer-review process.
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