Elsevier

The Lancet

Volume 377, Issue 9778, 14–20 May 2011, Pages 1655-1662
The Lancet

Articles
Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(11)60408-XGet rights and content

Summary

Background

Coated coils for endovascular treatment of cerebral aneurysm were developed to reduce recurrence and retreatment rates, and have been in clinical use for 8–9 years without robust evidence to determine their efficacy. We assessed the efficacy and safety of hydrogel-coated coils.

Methods

This randomised trial was undertaken in 24 centres in seven countries. Patients aged 18–75 years with a previously untreated ruptured or unruptured cerebral aneurysm of 2–25 mm in maximum diameter were randomly allocated (1:1) to aneurysm coiling with either hydrogel-coated coils or standard bare platinum coils (control). Randomisation was done with a computer-generated sequence, stratified by aneurysm size, shape, and dome-to-neck ratio; intention to use assist device; and by region. Participants and those assessing outcomes were masked to allocation. Analysis was by modified intention to treat (excluding missing data). Primary outcome was a composite of angiographic and clinical outcomes at 18-month follow-up. We also did prespecified subgroup analyses of characteristics likely to be relevant to angiographic outcome. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN30531382.

Findings

249 patients were allocated to the hydrogel coil group and 250 to the control group. In 44 of 467 patients for whom an 18-month composite primary outcome was unavailable, 6-month angiographic results were used. 70 (28%) patients in the hydrogel group and 90 (36%) control patients had an adverse composite primary outcome, giving an absolute reduction in the proportion of adverse composite primary outcomes with hydrogel of 7·0% (95% CI −1·6 to 15·5), odds ratio (OR) 0·73 (0·49–1·1, p=0·13). In a prespecified subgroup analysis in recently ruptured aneurysms, there were more adverse composite primary outcomes in the control group than in the hydrogel group—OR 2·08 (1·24–3·46, p=0·014). There were 8·6% fewer major angiographic recurrences in patients allocated to hydrogel coils—OR 0·7 (0·4–1·0, p=0·049). There were five cases of unexplained hydrocephalus in not-recently-ruptured aneurysms in the hydrogel coil group and one case in the control group.

Interpretation

Whether use of hydrogel coils reduces late aneurysm rupture or improves long-term clinical outcome is not clear, but our results indicate that their use lowers major recurrence.

Funding

MicroVention Inc.

Introduction

After the international subarachnoid aneurysm trial (ISAT), which showed better outcomes with endovascular coiling than with neurosurgical clipping for the treatment of intracranial aneurysms, endovascular coiling is the preferred treatment for many patients.1, 2, 3 The technique for endovascular coiling is described in the webappendix (p 1); see also webvideos 1–4). Although aneurysm clipping is a much more invasive procedure, aneurysm remnants or recurrences and the need for retreatment are more common after endovascular coiling than after clipping.2, 4, 5, 6 Major aneurysm recurrences (aneurysm incompletely occluded on follow-up imaging) occur after coiling in 15–19%4, 6, 7 of patients by 3–6 months after treatment, rising to 21% at a mean of 16 months after treatment.4 Therefore, follow-up imaging beyond 6 months is mandatory and important for the ongoing management of patients.8

The risk of haemorrhage from an aneurysm after coiling is very low at 0·12–0·4% per year.3, 9, 10 Retreatment rates after coiling are also low at 9–11% per year.3, 9 This low event rate means that randomised trials to assess whether a refinement of technology improves outcomes (especially haemorrhage) would need an unfeasibly large study population for what is, compared with cardiological interventions, a relatively low volume procedure. A surrogate endpoint for coiling outcome is therefore needed to assess whether technical advances improve outcomes.11 Major (angiographic) recurrence is a clinically relevant surrogate because angiographic follow-up directly affects management of patients. Major recurrence is associated with an increased risk of bleeding, and can lead to retreatment and more intense or extended imaging surveillance.6, 10, 11 An intervention that substantially reduced major recurrence rate would be expected to reduce the already low rebleed and retreatment rates10 and reduce the intensity and duration of imaging surveillance, which would be of clear benefit to patients and health-care systems.11 The externally validated angiographic scale (Montreal scale) used to assess recurrences in the Hydrocoil Endovascular aneurysm occLusion and Packing Study (HELPS) trial has high reproducibility and good to very good interobserver agreement (with mean κ for 3 point Montreal scale of 0·67).4, 12

Coated coils for aneurysm treatment have been in clinical use for 8–9 years at a much increased cost compared with bare platinum coils, and without robust evidence of their safety and effectiveness.13 The hydrogel-coated coil we used in HELPS was designed to improve aneurysm packing by coils, aiming to improve aneurysm stability and aneurysm neck healing,14, 15 with the added advantage of the use of substantially shorter coil length (webappendix p 3). We aimed to establish whether use of hydrogel-coated coils for treatment of intracranial aneurysms improves outcomes compared with use of bare platinum coils.

Section snippets

Patients

Patients were enrolled into HELPS, a pragmatic, multicentre, randomised controlled trial from 24 centres in seven countries (UK, USA, Brazil, Germany, Australia, France, and Argentina). Patients were eligible for inclusion if they presented with a previously untreated cerebral aneurysm measuring 2–25 mm in maximum diameter, were aged 18–75 years, were deemed by the neurovascular team to need coiling, were not pregnant, had a World Federation of Neurosurgeons grading between 0 and 3,16 had

Results

Patients were randomly assigned to treatment between September 13, 2004, and February 21, 2007 (figure 1). 12 centres kept detailed eligibility logs, which showed that 20% of screened patients were included in this trial, which is consistent with similar trials.1, 2, 3 One patient was inadvertently enrolled twice, and the second entry is not included in analyses. Patients' baseline characteristics and clinical demographics and protocol deviations, including crossovers and withdrawals, are

Discussion

We recorded no significant difference between patients in the HES and control groups when assessing the primary outcome—a composite of major angiographic recurrence and clinical status. However, when assessing only angiographic recurrence (on which the trial was powered), we recorded fewer angiographic recurrences in the HES group than in controls.

We noted little difference in clinical outcomes, bleed or rebleed, and re-treatment rates between the two treatment groups. As expected, the number

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