Dressings and topical agents (gels, ointments and creams) for treating venous leg ulcers

What is the aim of this review?

The aim of this review is to find out which dressings and topical agents (gels, ointments and creams) are most effective for treating a type of wound known as venous leg ulcers. These are long-term wounds in the lower leg caused by problems with blood flow back up the leg through the veins. Researchers from Cochrane found 78 relevant studies (randomised controlled trials) to answer this question. Randomised controlled trials are medical studies where patients are chosen at random to receive different treatments. This type of trial provides the most reliable evidence. We evaluated these studies using a method known as network meta-analysis (NMA), which allowed us to compare treatments across different studies and to rank them in terms of complete ulcer healing.

Key messages

We cannot be certain which dressings and topical agents are most effective for healing venous leg ulcers: over all studies there were not enough participants per treatment and there was high risk of bias; this means that many of the studies were conducted or reported in a way that means we cannot be sure if the results are accurate. The main treatment for venous leg ulcers is compression bandages or stockings and the choice of additional dressings or topical treatments should take into account the review findings and their uncertainty, alongside factors such as patient preference and cost.

What was studied in the review?

Venous leg ulcers are open wounds caused by poor blood flow through the veins of the lower leg. Increased pressure in the leg veins may cause damage to the skin and surrounding tissues, leading to an ulcer. Venous leg ulcers can be slow to heal and are painful and costly to treat. The main treatment is compression bandages or stockings but these are often combined with dressings (e.g. foam or nonadherent dressings) and topical creams, gels or ointments. We wished to know which of these additional treatments are most effective when it comes to ulcer healing.

What are the main results of the review?

We found 78 studies relevant to this question, dating from 1985 to 2016. The studies involved 7014 participants (a majority were women, and average age ranged from 46 to 81 where reported). Our NMA included 59 studies (5156 participants) and compared 25 different treatments such as hydrocolloid and silver-impregnated dressings and a variety of creams and gels.

Silver dressings may increase the probability of venous leg ulcer healing compared with nonadherent dressings. However, in the light of the rest of the NMA evidence, we cannot be very confident about any conclusion, and the network as a whole represents low-certainty evidence. This was due to the small numbers of people involved across all included studies, the small number of studies focusing on each treatment, and the high risk of bias. We cannot therefore be certain which are the most effective treatments for venous leg ulcers, or even which treatments it would be best to compare in future trials.

How up to date is this review?

We searched for studies published up to March 2017.

Authors' conclusions: 

More research is needed to determine whether particular dressings or topical agents improve the probability of healing of venous leg ulcers. However, the NMA is uninformative regarding which interventions might best be included in a large trial, largely because of the low certainty of the whole network and of individual comparisons.The results of this NMA focus exclusively on complete healing; whilst this is of key importance to people living with venous leg ulcers, clinicians may wish to take into account other patient-important outcomes and factors such as patient preference and cost.

Read the full abstract...
Background: 

Venous leg ulcers are open skin wounds on the lower leg which can be slow to heal, and are both painful and costly. The point prevalence of open venous leg ulcers in the UK is about 3 cases per 10,000 people, and many people experience recurrent episodes of prolonged ulceration. First-line treatment for venous leg ulcers is compression therapy, but a wide range of dressings and topical treatments are also used. This diversity of treatments makes evidence-based decision-making challenging, and a clear and current overview of all the evidence is required. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents.

Objectives: 

To assess the effects of (1) dressings and (2) topical agents for healing venous leg ulcers in any care setting and to rank treatments in order of effectiveness, with assessment of uncertainty and evidence quality.

Search strategy: 

In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. We updated this search in March 2018; as a result several studies are awaiting classification.

Selection criteria: 

We included published or unpublished randomised controlled trials (RCTs) that enrolled adults with venous leg ulcers and compared the effects of at least one of the following interventions with any other intervention in the treatment of venous leg ulcers: any dressing, or any topical agent applied directly to an open venous leg ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factors and other biological agents, larval therapy and treatments such as laser, heat or ultrasound. Studies were required to report complete wound healing to be eligible.

Data collection and analysis: 

Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We conducted this NMA using frequentist meta-regression methods for the efficacy outcome; the probability of complete healing. We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals (CIs) for individual treatments focusing on comparisons with widely used dressing classes, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole.

Main results: 

We included 78 RCTs (7014 participants) in this review. Of these, 59 studies (5156 participants, 25 different interventions) were included in the NMA; resulting in 40 direct contrasts which informed 300 mixed-treatment contrasts.

The evidence for the network as a whole was of low certainty. This judgement was based on the sparsity of the network leading to imprecision and the general high risk of bias in the included studies. Sensitivity analyses also demonstrated instability in key aspects of the network and results are reported for the extended sensitivity analysis. Evidence for individual contrasts was mainly judged to be low or very low certainty.

The uncertainty was perpetuated when the results were considered by ranking the treatments in terms of the probability that they were the most effective for ulcer healing, with many treatments having similar, low, probabilities of being the best treatment. The two most highly-ranked treatments both had more than 50% probability of being the best (sucralfate and silver dressings). However, the data for sucralfate was from one small study, which means that this finding should be interpreted with caution. When exploring the data for silver and sucralfate compared with widely-used dressing classes, there was some evidence that silver dressings may increase the probability of venous leg ulcer healing, compared with nonadherent dressings: RR 2.43, 95% CI 1.58 to 3.74 (moderate-certainty evidence in the context of a low-certainty network). For all other combinations of these five interventions it was unclear whether the intervention increased the probability of healing; in each case this was low- or very low-certainty evidence as a consequence of one or more of imprecision, risk of bias and inconsistency.

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