SIGNET will be one of the largest prospective donor studies in the world, positioned perfectly to coordinate the unique strengths of the UK NHS infrastructure as well as the expertise and facilities available here in Newcastle.

Many potential organs for donation, particularly the heart and lungs, are damaged in the donor. The process of removal and re-attachment in the recipient can exacerbate this damage. As a result, by no means all the organs offered can be used for transplant. Current estimates suggest that this is the worst for hearts and lungs, where only 20-25% of those offered can be used.

A number of additions to the care of the donor could minimise or reverse this damage and these additions might be of real benefit to the recipients of all organs.

SIGNET is designed to explore this issue via analysis of the 'statin' group of drugs. Statins are widely used as cholesterol lowering agents, but may have other benefits many of which revolve around reducing 'inflammation', which is often the root cause of damage to organs in both a donor and a recipient.  

SIGNET will aim to recruit 2600 adult organ donors, over 4 years, to be randomized after consent for donation and research, to receive Simvastatin 80mg as a single dose

The main focus of the study will be to look for an improvement in complications and survival in heart transplant recipients, though the trial also presents an opportunity to look at the potential benefits in all organs.

Over 80 sites will be used during the duration of the trial and the UK is ideally placed to explore these options in a national, and scientifically robust way. 

Expected outcomes

The team anticipate the primary outcome will be a composite of mortality, cardiac mechanical support or renal replacement therapy within 30 days following heart transplant.

Secondary outcomes are important clinical and safety organ specific transplant outcomes routinely collected by the UK Transplant Registry for all solid organs transplanted from donors in the study.

Recruitment will begin in April 2021. Analysis of consent and inclusion will be continuous, with a formal internal pilot phase to the end of year 1.

Planned interim analysis will be at two and three years for harm, benefit and futility. Recruitment will run for a total of 48 months, followed by a 12 month follow up period for collection of all organ primary and secondary outcomes. 

Final analyses and preparation of the final report will be completed by June 2026.

Furthermore, SIGNET is another UK first in that it has close links to the newly launched UK Organ Donation and Transplantation Network (UKODTRN)

The trial team anticipate this collaboration will both support this work and allow them to build on these links for future donor-intervention and organ transplant studies.

The Study Team for SIGNET are as follows:
Lead Co-applicants:
John Dark (Newcastle University) and Dan Harvey (Nottingham University Hospitals)
Co-applicants:
For individual Organ groups, from Newcastle:
Guy MacGowan (Heart)
Andy Fisher (Lung)
Neil Sheerin (Kidney)
Jim Shaw (Pancreas)
Chris Watson (Liver) joins the team from Cambridge
For CTU:
Alison Deary, Helen Thomas (Statistics)
Representing PPI:
Andrea Fallow, Hilary Yates
Trial Management: 
Claire Foley, Clinical Operations Manager
Amy Evans, Clinical Trial Manager

For further information, please email the SIGNET team

Visit the trial SIGNET website