Rescap to prevent surgical complications in open-heart surgery
Research type
Research Study
Full title
Preventing oxidative stress-induced ischaemic injury and systemic inflammation complications during and after invasive cardiac surgery with alkaline phosphatase (APPIRED III)
IRAS ID
286267
Contact name
Ruud Brands
Contact email
Sponsor organisation
Alloksys Life Sciences BV
Eudract number
2016-002663-33
ISRCTN Number
ISRCTN03050476
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 5 months, 1 days
Research summary
Alkaline Phosphatase (ALP) is a natural human enzyme which protects against shock and organ failure resulting from uncontrolled activation of the immune system after infection, injury and inflammation (cytokine storm or Systemic Inflammatory Syndrome, SIRS). It is normally present in blood, gut, liver, lung, placenta and bone. During shock ALP is consumed with insufficient to maintain normal physiological protection. Animal and human experimental studies show that giving ALP can stop the cascade of inflammatory messengers (cytokines) and there is evidence of kidney protection and reduced mortality in septic (bacterial) shock.
Patients recovering from open cardiac surgery frequently experience SIRS syndrome resulting in ICU care, kidney damage, delayed recovery and mortality which can approach 10% in cases with high pre-surgical risk scores (EuroSCORE II ≥ 3). APPIRED II, placebo-controlled phase 2 study of protection after cardiac surgery showed expected results with trends to reduction of adverse outcomes including mortality.
APPIRED III is a multinational, placebo-controlled trial of protection from renal damage, gut and brain complications and mortality after cardiac surgeries in patients with high presurgical risk scores (Euroscore>3). The treatment is IV injection of 1000IU of ALP and then infusion of 9000IU over 24hrs, replacing the normal physiological quantities of ALP consumed during surgery and cardiac bypass.
There are no known adverse effects from physiological replenishment of ALP and there have been no treatment emergent AE’s or SAE’s in phase 1, phase2 or in the activity of the APPIRED III study to date.
The trial is approved(EudraCT no. 2016-002663-33, ISRCTN 03050476), is open in 16 sites worldwide with 160 cases enrolled. After an interim safety analysis at 250 cases it aims to recruit 1250 cases divided 1:1 active and placebo. Papworth Hospital will be the first UK site to collaborate.REC name
London - London Bridge Research Ethics Committee
REC reference
21/LO/0085
Date of REC Opinion
2 Feb 2021
REC opinion
Unfavourable Opinion