The purpose of this study (APPIRED III) is to investigate the efficacy of administered prophylactically RESCAP with regard to the prevention of (severe) renal failure, or renal dysfunction, reducing morbidity and mortality. It also looks at systemic…
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
This study has a so-called composite outcome, with a combination of the
parameters described below at OR/OR level:
Reduction of actual morbidity and mortality numbers.
OR
Reduction of the post-surgical complications such as AKI, acute renal failure
by intravenous administration of RESCAP (alkaline phosphatase) in comparison
with the placebo-group. Reduction will be measured to known blood parameters
and renal function parameters, AKIN > 2 ( Rise in serum creatinine of by 0.3
mg/dl or 26 µmol/L in 48 hours/ a percentage increase in the serum creatinine
concentration of >=50 percent 10 or a drop in urine output to 0.5 ml/kg/hour for
6 hours)
OR
demonstrate that time to extubation [ defined as removal of endotracheal tube]
is reduced
OR
reduce GI Complications : defined as demonstrable nasogastric bleeding > 12
hours , malena or positive fecal occult blood
OR
reduce neurological complications : defined as focal neurological deficit of
central origin lasting more than 72 hours demonstrable on a CT scan.
Secondary outcome
outcomes associated to CPB and AP intervention including
1) the incidence of renal replacement therapy, b) duration of renal replacement
therapy, c) days spent in the
ICU and time spent in hospital, and d) the incidence of arrhythmias in the two
groups
2) Plasma levels of a set of inflammatory markers (IL-6, IL-8, IL-10,
TNF-alpha) and increase endogenous alkaline phosphatase levels and kidney
function markers (IL18, NGAL, TIMP-1, GFR) in the control and AP treated groups.
3. Following the finalisation of APPIRED III study: Estimate the incremental
cost effectiveness ratio (ICER) by comparing the costs and effectiveness
between AP and placebo groups.
Background summary
Cardiac surgery-associated acute kidney injury (AKI) is a common and serious
post-operative complication of cardiac surgery that employs cardiopulmonary
bypass (CPB), and it is the second most common cause of AKI in the intensive
care unit (ICU). It is estimated that post-operative acute kidney injury (AKI)
increases the risk of mortality three to eight times in cardiac surgery
patients This AKI is characterized by an abrupt deterioration in kidney
function following cardiac surgery as evidenced by a reduction in the
glomerular filtration rate. Approximately 1-3% of all patients on CPB will
require permanent renal replacement therapy Permanent dialysis is not only a
costly complication, it also significantly impacts the quality of life and
reduces the number of years a patient lives after their operation.
During the APPIRED I and II study we demonstrated that intervention with RESCAP
benefits can include reduced inflammation, as well as reduced morbidity and
mortality . Due to the small size of the number of patients included ( ca 100)
RESCAP will now be examined in a multicenter study whether these results can be
confirmed. Since the main complication of open-heart action surgery renal
dysfunction, possibly even acute renal failure, and RESCAP intervention has now
been demonstrated in another group of patients with septic shock that the
kidney function is greatly improved, it is to be expected that also in this
open-heart surgery patients may be observed, these effects of RESCAP. To this
end, in order to also clinically significant rulings do a cohort of 1250
patients necessary.
Study objective
The purpose of this study (APPIRED III) is to investigate the efficacy of
administered prophylactically RESCAP with regard to the prevention of (severe)
renal failure, or renal dysfunction, reducing morbidity and mortality. It also
looks at systemic inflammation (inflammation) and the effects of subsequent
treatment with RESCAP, an anti-inflammatory drug.
RESCAP intervention is expected to reduce the overall morbidity and will also
be able to decrease the mortality rate in the group of RESCAP-treated patients.
Reported elsewhere is that a reduction in renal function (Acute Kidney Injury /
AKI) during or after the operation is predictive to for a poorer post-surgical
quality of life and overall long-term survival. Renal impairment, we hope to
prevent with RESCAP intervention, in this group of open-heart surgery patients
at increased risk of complications (EUROSCORE II greater or equal 3))
Study design
Multicenter study, prospective, randomized, double-blind, placebo-controlled
intervention study.
Study burden and risks
To date, there are no risks identified in administering RESCAP intravenously.
The APPIRED I study, 63 patients were included. No serious adverse effects of
RESCAP documented. In the APPIRED II study with a total of 52 patients also no
serious adverse events were observed. Data are included in the investigator
brochure.
The study burden for patients will include the taking of blood samples up to 5
days after the operation. These can be taken for the most part from the lines
already present, or will be taken at times when also routine blood samples are
taken. The bolus, as well as the 24-hour infusion can be injected into already
affixed intravenous accesses. Patients will be called 30 days after the
operation and data on medication use and adverse events will be collected.
Agro Business Park 10
Wageningen 6708 PW
NL
Agro Business Park 10
Wageningen 6708 PW
NL
Listed location countries
Age
Inclusion criteria
A potential subject must meet all of the following criteria to participate in the study:
1. greater than 21 years of age (legal adult in Singapore)
2. Undergoing cardiac surgery with planned cardiopulmonary bypass
3. EUROSCORE II greater than or equal 3
4. Ability to provide informed consent (not incapacitated)
Exclusion criteria
Any subjects meeting the following criteria at baseline will be excluded:
1. Already on renal replacement therapy
2. Patients with chronic kidney disease defined as urinary albumin excretion of >=30 mg/day, or equivalent or estimated glomerular filtration rate lower than 60 ml/min/1.73 m2 ( CKD stage > 2)
3. Patients who are pregnant
4. Concurrent enrolment in another clinical trial
5. Known allergic reaction to bovine alkaline phosphatase
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002663-33-NL |
| CCMO | NL59364.100.16 |