TY - JOUR

T1 - Silver-impregnated, antibiotic-impregnated or non-impregnated ventriculoperitoneal shunts to prevent shunt infection: the BASICS three-arm RCT

AU - Mallucci, C.L.

AU - Jenkinson, Michael

AU - Conroy, Elizabeth J.

AU - Hartley, John C.

AU - Brown, Michaela

AU - Moitt, Tracey

AU - Dalton, Joanne

AU - Kearns, Tom

AU - Griffiths, Michael J.

AU - Culeddu, Giovanna

AU - Solomon, Tom

AU - Hughes, Dyfrig

AU - Gamble, Carrol

PY - 2020/4/2

Y1 - 2020/4/2

N2 - BACKGROUND: Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life.OBJECTIVES: The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.g. impregnated with rifampicin and clindamycin) or silver-impregnated ventriculoperitoneal shunts (hereafter referred to as silver shunts) reduce infection compared with standard ventriculoperitoneal shunts (hereafter referred to as standard shunts).DESIGN: This was a three-arm, superiority, multicentre, parallel-group randomised controlled trial. Patients and a central primary outcome review panel, but not surgeons or operating staff, were blinded to the type of ventriculoperitoneal shunt inserted.SETTING: The trial was set in 21 neurosurgical wards across the UK and the Republic of Ireland.PARTICIPANTS: Participants were patients with hydrocephalus of any aetiology who were undergoing insertion of their first ventriculoperitoneal shunt.INTERVENTIONS: Participants were allocated 1 : 1 : 1 by pressure-sealed envelope to receive a standard non-impregnated, silver-impregnated or antibiotic-impregnated ventriculoperitoneal shunt at the time of insertion. Ventriculoperitoneal shunts are medical devices, and were used in accordance with the manufacturer's instructions for their intended purpose.MAIN OUTCOME MEASURES: The primary outcome was time to ventriculoperitoneal shunt failure due to infection. Secondary outcomes were time to failure for any cause, reason for failure (infection, mechanical), types of ventriculoperitoneal shunt infection, rate of infection after first clean (non-infected) revision and health economics. Outcomes were analysed by intention to treat.RESULTS: Between 26 June 2013 and 9 October 2017, 1605 patients from neonate to 91 years of age were randomised to the trial: n  = 36 to the standard shunt, n  = 538 to the antibiotic shunt and n  = 531 to the silver shunt. Patients who did not receive a ventriculoperitoneal shunt ( n  = 4) or who had an infection at the time of insertion ( n  = 7) were not assessed for the primary outcome. Infection occurred in 6.0% ( n  = 32/533) of those who received the standard shunt, in 2.2% ( n  = 12/535) of those who received the antibiotic shunt and in 5.9% ( n  = 31/526) of those who received the silver shunt. Compared with the standard shunt, antibiotic shunts were associated with a lower rate of infection (cause-specific hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80) and a decreased probability of infection (subdistribution hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80). Silver shunts were not associated with a lower rate of infection than standard shunts (cause-specific hazard ratio 0.99, 97.5% confidence interval 0.56 to 1.74). The ventriculoperitoneal shunt failure rate attributable to any cause was 25.0% overall and did not differ between arms. Antibiotic shunts save £135,753 per infection avoided. There were no serious adverse events. LIMITATIONS: It was not possible to blind treating neurosurgeons to the ventriculoperitoneal shunt type. The return rate for patient-reported outcomes was low. Limitations to the economic evaluation included failure to obtain Hospital Episode Statistics data from NHS Digital, as per protocol. Reliance on patient-level information and costing systems data mitigated these limitations.CONCLUSIONS: Antibiotic shunts have a reduced infection rate compared with standard shunts, whereas silver shunts do not. Antibiotic shunts are cost-saving.FUTURE WORK: A sample collection has been established that will enable the study of surrogate markers of ventriculoperitoneal shunt infection in cerebrospinal fluid or blood using molecular techniques. A post hoc analysis to study factors related to shunt failure will be performed as part of a future study. An impact analysis to assess change in practice is planned.TRIAL REGISTRATION: Current Controlled Trials ISRCTN49474281.FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 17. See the NIHR Journals Library website for further project information.

AB - BACKGROUND: Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life.OBJECTIVES: The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.g. impregnated with rifampicin and clindamycin) or silver-impregnated ventriculoperitoneal shunts (hereafter referred to as silver shunts) reduce infection compared with standard ventriculoperitoneal shunts (hereafter referred to as standard shunts).DESIGN: This was a three-arm, superiority, multicentre, parallel-group randomised controlled trial. Patients and a central primary outcome review panel, but not surgeons or operating staff, were blinded to the type of ventriculoperitoneal shunt inserted.SETTING: The trial was set in 21 neurosurgical wards across the UK and the Republic of Ireland.PARTICIPANTS: Participants were patients with hydrocephalus of any aetiology who were undergoing insertion of their first ventriculoperitoneal shunt.INTERVENTIONS: Participants were allocated 1 : 1 : 1 by pressure-sealed envelope to receive a standard non-impregnated, silver-impregnated or antibiotic-impregnated ventriculoperitoneal shunt at the time of insertion. Ventriculoperitoneal shunts are medical devices, and were used in accordance with the manufacturer's instructions for their intended purpose.MAIN OUTCOME MEASURES: The primary outcome was time to ventriculoperitoneal shunt failure due to infection. Secondary outcomes were time to failure for any cause, reason for failure (infection, mechanical), types of ventriculoperitoneal shunt infection, rate of infection after first clean (non-infected) revision and health economics. Outcomes were analysed by intention to treat.RESULTS: Between 26 June 2013 and 9 October 2017, 1605 patients from neonate to 91 years of age were randomised to the trial: n  = 36 to the standard shunt, n  = 538 to the antibiotic shunt and n  = 531 to the silver shunt. Patients who did not receive a ventriculoperitoneal shunt ( n  = 4) or who had an infection at the time of insertion ( n  = 7) were not assessed for the primary outcome. Infection occurred in 6.0% ( n  = 32/533) of those who received the standard shunt, in 2.2% ( n  = 12/535) of those who received the antibiotic shunt and in 5.9% ( n  = 31/526) of those who received the silver shunt. Compared with the standard shunt, antibiotic shunts were associated with a lower rate of infection (cause-specific hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80) and a decreased probability of infection (subdistribution hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80). Silver shunts were not associated with a lower rate of infection than standard shunts (cause-specific hazard ratio 0.99, 97.5% confidence interval 0.56 to 1.74). The ventriculoperitoneal shunt failure rate attributable to any cause was 25.0% overall and did not differ between arms. Antibiotic shunts save £135,753 per infection avoided. There were no serious adverse events. LIMITATIONS: It was not possible to blind treating neurosurgeons to the ventriculoperitoneal shunt type. The return rate for patient-reported outcomes was low. Limitations to the economic evaluation included failure to obtain Hospital Episode Statistics data from NHS Digital, as per protocol. Reliance on patient-level information and costing systems data mitigated these limitations.CONCLUSIONS: Antibiotic shunts have a reduced infection rate compared with standard shunts, whereas silver shunts do not. Antibiotic shunts are cost-saving.FUTURE WORK: A sample collection has been established that will enable the study of surrogate markers of ventriculoperitoneal shunt infection in cerebrospinal fluid or blood using molecular techniques. A post hoc analysis to study factors related to shunt failure will be performed as part of a future study. An impact analysis to assess change in practice is planned.TRIAL REGISTRATION: Current Controlled Trials ISRCTN49474281.FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 17. See the NIHR Journals Library website for further project information.

U2 - 10.3310/hta24170

DO - 10.3310/hta24170

M3 - Article

C2 - 32238262

VL - 24

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 17

ER -