What is the research question?
Does the choice of topical agents (creams or ointments) or wound dressings affect the healing of arterial leg ulcers?
Background
People with blood circulation problems in their legs can develop leg ulcers, with adults having around a 1% chance of suffering from a leg ulcer at some time in their life. The majority of ulcers (around 70%), result from poor blood flow in the veins and are called venous leg ulcers. These are generally treated by compression. Arterial leg ulcers (around 22% of ulcers) occur because of poor blood supply to the legs, when there is a block in a leg artery or narrowing of the arteries (atherosclerosis). Without treatment of the underlying poor arterial blood supply, ulcers take a long time to heal or may even never heal. These ulcers are treated to promote healing and protect from infection, by covering them with dressings or using topical agents, or both. A variety of types of dressings can be used, depending on whether the main intention is to treat infection, reduce ulcer pain, or manage the fluid that can leak from these ulcers (exudate), and so promote healing.
Study characteristics and key results
We found two small studies that presented data for 49 participants with arterial leg ulcers (search conducted January 2019). The studies also included participants with other kinds of ulcers, and it is not clear what proportion of participants were diabetic. Neither study described the methods fully, both presented limited results for the arterial ulcer participants, and one study did not provide information on the number of participants with an arterial ulcer in the control group. The follow-up periods (six and eight weeks) were too short to measure healing. Therefore, the data that were available were incomplete and cannot be generalised to the greater population of people who suffer from arterial leg ulcers.
One study randomised participants to either 2% ketanserin ointment in polyethylene glycol (PEG) or PEG alone, administered twice a day over eight weeks. This study reported increased wound healing in the ketanserin group, when compared with the control group. It should be noted that ketanserin is not licensed for use in humans in all countries.
The second study randomised participants to either topically-applied growth factors isolated from the participant's own blood (concentrated growth factors (CGF)), or standard dressing; both applied weekly for six weeks. This study reported that 66.6% of CGF-treated diabetic arterial ulcers showed more than a 50% decrease in ulcer size, compared to 6.7% of non-healing ulcers treated with standard dressing.
Only one study mentioned side effects, and reported that no participant experienced side effects during follow-up (six weeks). Neither of the two studies reported time to ulcer healing, patient satisfaction or quality of life measures.
Certainty of the evidence
There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers. We downgraded the overall certainty of the available evidence to 'very low' and 'low', because the studies reported their methods poorly, there were only two studies and few participants with arterial disease, and because the studies were short and reported few results. This made it impossible to determine whether there was any real difference in the number of ulcers healed between the groups.
There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers.
It is estimated that up to 1% of people in high-income countries suffer from a leg ulcer at some time in their life. The majority of leg ulcers are associated with circulation problems; poor blood return in the veins causes venous ulcers (around 70% of ulcers) and poor blood supply to the legs causes arterial ulcers (around 22% of ulcers). Treatment of arterial leg ulcers is directed towards correcting poor arterial blood supply, for example by correcting arterial blockages (either surgically or pharmaceutically). If the blood supply has been restored, these arterial ulcers can heal following principles of good wound-care. Dressings and topical agents make up a part of good wound-care for arterial ulcers, but there are many products available, and it is unclear what impact these have on ulcer healing. This is the third update of a review first published in 2003.
To determine whether topical agents and wound dressings affect healing in arterial ulcers. To compare healing rates and patient-centred outcomes between wound dressings and topical agents.
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 28 January 2019.
Randomised controlled trials (RCTs), or controlled clinical trials (CCTs) evaluating dressings and topical agents in the treatment of arterial leg ulcers were eligible for inclusion. We included participants with arterial leg ulcers irrespective of method of diagnosis. Trials that included participants with mixed arterio-venous disease and diabetes were eligible for inclusion if they presented results separately for the different groups. All wound dressings and topical agents were eligible for inclusion in this review. We excluded trials which did not report on at least one of the primary outcomes (time to healing, proportion completely healed, or change in ulcer area).
Two review authors independently extracted information on the participants' characteristics, the interventions, and outcomes using a standardised data extraction form. Review authors resolved any disagreements through discussion. We presented the data narratively due to differences in the included trials. We used GRADE to assess the certainty of the evidence.
Two trials met the inclusion criteria. One compared 2% ketanserin ointment in polyethylene glycol (PEG) with PEG alone, used twice a day by 40 participants with arterial leg ulcers, for eight weeks or until healing, whichever was sooner. One compared topical application of blood-derived concentrated growth factor (CGF) with standard dressing (polyurethane film or foam); both applied weekly for six weeks by 61 participants with non-healing ulcers (venous, diabetic arterial, neuropathic, traumatic, or vasculitic). Both trials were small, reported results inadequately, and were of low methodological quality. Short follow-up times (six and eight weeks) meant it would be difficult to capture sufficient healing events to allow us to make comparisons between treatments.
One trial demonstrated accelerated wound healing in the ketanserin group compared with the control group. In the trial that compared CGF with standard dressings, the number of participants with diabetic arterial ulcers were only reported in the CGF group (9/31), and the number of participants with diabetic arterial ulcers and their data were not reported separately for the standard dressing group. In the CGF group, 66.6% (6/9) of diabetic arterial ulcers showed more than a 50% decrease in ulcer size compared to 6.7% (2/30) of non-healing ulcers treated with standard dressing. We assessed this as very-low certainty evidence due to the small number of studies and arterial ulcer participants, inadequate reporting of methodology and data, and short follow-up period.
Only one trial reported side effects (complications), stating that no participant experienced these during follow-up (six weeks, low-certainty evidence). It should also be noted that ketanserin is not licensed in all countries for use in humans. Neither study reported time to ulcer healing, patient satisfaction or quality of life.