Efficacy and safety of programmable compared with fixed anti-siphon devices for treating idiopathic normal-pressure hydrocephalus (iNPH) in adults - SYGRAVA: study protocol for a randomized trial

Abstract

Background: Idiopathic normal-pressure hydrocephalus (iNPH) is a distinct form of dementia, characterized by gait ataxia, cognitive impairment and urinary incontinence. In contrast to all other causes of dementia (e.g., Alzheimer-type and others), ventriculoperitoneal (VP) shunt surgery may offer a curative treatment option to patients. While being a rather low-risk type of surgery, it may cause significant over- or underdrainage complications (e.g., headaches, dizziness, vomiting, intracerebral bleeding, etc.) during posture change. Anti-siphon devices (ASDs) are a group of technically different additional valves used in shunt surgery. They are designed to maintain intraventricular pressure within a normal physiological range regardless of patient position. Fixed ASDs proved to substantially lower the rate of overdrainage complications. No significant differences, however, were noted regarding underdrainage complications. Technical successors of fixed ASDs are programmable ASDs. The aim of this study is to evaluate whether programmable ASDs compared to fixed ASDs are able to avoid both over- and underdrainage complications.

Methods/design: In this investigator-initiated, multicenter randomized trial, 306 patients are planned to be recruited. Male and female patients aged ≥18 years with iNPH who are eligible for VP shunt surgery and meet all other entry criteria can participate. Patients will be randomized in a balanced 1: 1 fashion to a VP shunt with a programmable valve either supplemented with a fixed ASD, or a programmable ASD. Patients will be followed-up 3, 6 and, on an optional basis, 12 months after surgery. The primary outcome measure is the cumulative incidence of over- or underdrainage 6 months post surgery, as defined by clinical and imaging parameters.

Discussion: SYGRAVA is the first randomized trial to determine whether programmable ASDs reduce complications of drainage compared to fixed ASDs in patients with iNPH. The results of this study may contribute to health-technology assessment of different valve systems used for VP-shunt surgery, and determination of the future standard of care.

Trial registration: International Standard Randomised Controlled Trial Number: ISRCTN13838310 . Registered on 10 November 2016.

Keywords: Dementia; Idiopathic normal-pressure hydrocephalus; Programmable anti-siphon device; Randomized trial; Ventriculoperitoneal shunt.

Fig. 1

Types of anti-siphon devices (ASDs) – programmable ASD and fixed ASD (pressure-flow-controlled, flow-controlled and gravity-controlled)

Fig. 2

Trial flow diagram

Fig. 3

Pressure-flow curves of the adjustment settings of the Codman CERTAS plus valve® (a) and of the Medtronic PS Medical STRATA II® valve (b) modified according to (a) Codman CERTAS plus brochure DSUS/COD/1214/0229a 01/15 and (b) Medtronic PS Med STRATA II instructions for use 16,417-1H 30,329

Fig. 4

Schedule of enrollment, interventions and assessments