Recruitment problems prompt change in SPACE-2 protocol

Gustav Fraedrich

The protocol of the ongoing SPACE-2 (Stent-protected angioplasty in asymptomatic carotid stenosis vs. endarterectomy) study has recently changed from a three-arm design to a double two-arm design (SPACE-2A and 2B). Study investigator Gustav Fraedrich (director of the University Clinic of Vascular Surgery, University Hospital Innsbruck, Innsbruck, Austria) speaks to NeuroNews about the reasons for the change.

What are the objectives of the SPACE-2 study?

The aim of the SPACE-2 study is to assess if best medical therapy plus intervention (carotid endarterectomy or carotid stenting) in patients with asymptomatic carotid stenosis is superior to best medical therapy alone. A secondary endpoint will be to compare carotid stenting with carotid endarterectomy.

Initially, SPACE-2 was a designed as a three-arm study in which patients would be randomised to receive best medical therapy alone, best medical therapy plus carotid endarterectomy, or best medical therapy plus carotid stenting. However, in the new two-arm protocol, patients are randomised to receive best medical therapy alone or best medical therapy plus intervention (carotid endarterectomy or carotid stenting).

Why has the protocol of the study changed?

It was very difficult to communicate the three-arm nature of the study to patients and, also, we had to exclude centres that were not able to offer both stenting and endarterectomy. Now in this two-arm study, centres that only offer one of these interventions can participate and it is easier for patients to understand the choices available to them (best medical therapy or intervention) and give their consent to be randomised. 

What is the best
medical therapy being used in the study?

A combination of antiplatelets, antihypertensives, and statins, but it can be individualised for the patient. If the concept of what constitutes “best medical therapy” changes, the best medical therapy will be changed in both arms as one is best medical therapy alone and the other is best medical therapy plus intervention.

What is the recruitment target for the study?

We need to recruit 3,600 patients and at the moment (after more than two years), we have 400 enrolled. We hope that the recruitment process will be faster now that we have changed the protocol. 

What is the follow-up period?

As the rate of stroke is less than 1% per year in asymptomatic patients (treated with best medical therapy alone), the follow-up period needs to be long. Therefore for the primary endpoint (superiority of intervention plus medical therapy vs. medical therapy alone), the follow-up period is five years. 

If new centres are interested in being involved in the study, what do they need to offer?

The specialists working at the centre need to be certified, and this means that every interventionalist and every surgeon hoping to be involved in the study needs to have each done 40 documented procedures (carotid stenting or carotid endarterectomy) within the past two years. The information on these procedures is given to the safety committee, who can then certify the interventionalist or surgeon.