To assess safety and tolerability of EA-230 in patients undergoing cardiac surgery with cardiopulmonary bypass.To assess the anti-inflammatory effects of EA-230 in patients with systemic inflammation following cardiac surgery. To assess the effects…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety:
• Adverse events
• Vital signs (blood pressure and heart rate)
• Safety laboratory parameters (Hb, Ht, leucocytes, thrombocytes, leucocyte
differential blood count, sodium, potassium, creatinine, urea, alkaline
phosphatase, ALT, AST, γGT, CK, CRP)
Secondary outcome
• Blood plasma levels of IL-6
• GFR measured by plasma clearance of iohexol
Inflammatory
• Plasma levels of other cytokines: TNFα, IL-8, IL-10, IL-1RA, MCP-1, IL12-p70,
MIP1α , MIP1β
• Body temperature
• SIRS score
• SOFA score
Outcome
• Length of stay (ICU and general)
• 28-day and 90 days mortality
• Apache score
• Major clinical events (stroke, myocardial infarction, rethoracotomy)
Renal:
• Endogenous creatinine clearance (ECC) using urine and plasma creatinine
• Urine markers: KIM-1, NGAL, L-FABP, TIMP-2*IGFBP-7
• Urine output (per 4 hrs during ICU-length of stay)
• Urine biochemistry: Urea, sodium, Creatinine
• Incidence of AKI stages, according to RIFLE-criteria
• Need for Renal replacement therapy (RRT) and days of RRT
Cardiovascular
• Vasopressor use, expressed as inotropic score
• Fluid therapy
Pulmonary
• Time until detubation
• A-a O2 gradient
Pharmacokinetics
• Blood plasma levels of EA-230 and, AUC, Cmax, terminal t1/2, Cl, V.
Background summary
EA-230 is a newly developed synthetic compound with anti-inflammatory
properties, it is a linear tetrapeptide derived from the human chorionic
gonadotropin hormone (hCG). Recently, its immunomodulatory effects in humans
were confirmed in a phase I trial and an optimal dose was established. To
establish this anti-inflammatory effect in a selected patient population and
assess clinical outcome, a phase IIb trial will be conducted with patients
undergoing cardiac surgery.
Study objective
To assess safety and tolerability of EA-230 in patients undergoing cardiac
surgery with cardiopulmonary bypass.
To assess the anti-inflammatory effects of EA-230 in patients with systemic
inflammation following cardiac surgery.
To assess the effects of EA-230 on clinical outcomes in this patient group
Study design
Randomized, placebo-controlled, double blind clinical phase IIb study.
Intervention
160 patients:
Active group:
EA-230 treatment: EA-230 90 mg/kg/hour continuous i.v infusion for a maximum
of 4 hours during surgery, n=80.
Placebo group:
Placebo treatment: NaCl continuous i.v infusion for a maximum of 4 hours
during surgery, n= 80.
Study burden and risks
A previously performed phase I study into the safety and tolerability of EA-230
showed that administration of EA-230 up to 90 mg/kg/hour infused intravenously
for 2 hours is well tolerated and has an excellent safety profile. In a
subsequently executed phase IIa study this safety profile (using the same
dosages) was confirmed in a model of systemic inflammation. No study
drug-related adverse events were observed.
Our previous phase I and IIa studies showed stable plasma levels throughout the
2-hour infusion period. Steady state levels were already reached after 15
minutes of infusion with an associated half life of approximately 5 minutes.
Although the duration of infusion in this study may exceed 2 hours due to
extended duration of the surgical procedure, infusion is kept constant at a
rate of 90 mg/kg/hour and will therefore not exceed previous measured plasma
levels. The maximum duration of infusion is 4 hours. Stopping of infusion will
result in very rapid decline in plasma levels of the IMP if adverse events
related to IMP infusion are suspected.
A non-nephrotoxic, low dose of 5 mL iohexol (240 mg I/ml) will be administered
in all patients, except in those with a known allergy.
Blood withdrawal during the study is restricted to a volume of less than 100 mL
and is not associated with risks. Venipuntures pre- and post-operative carries
the risk of hematomae at the puncture sites.
In conclusion the risks of participation in the trial are negligible according
to the criteria of the NFU.
Kneuterdijk 2
Den Haag 2514EN
NL
Kneuterdijk 2
Den Haag 2514EN
NL
Listed location countries
Age
Inclusion criteria
1. Patients scheduled for elective on-pump CABG surgery, with or without valve replacement;2. Written informed consent to participate in this trial prior to any study-mandated procedure.;3. Patients aged >18 years, both male and female.;4. Patients have to agree to use a reliable way of contraception with their partners from study entry until 3 months after study drug administration.
Exclusion criteria
1. Immune compromised;• Solid organ transplantation;• Known HIV;• Pregnancy;• Systemic use of immunosuppressive drugs;2. Non-elective/Emergency surgery;3. Hematological disorders;• Known disorders from myeloid and/or lymphoid origin;• Leucopenia (leucocyte count < 4x10^9/L);4. Use of iohexol contrast <48 hours before start of the first study procedure ;5. Known hypersensitivity to any excipients of the drug formulations used;6. Treatment with investigational drugs or participation in any other intervention clinical trial within 30 days prior to study drug administration;7. Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) ;8. Known or suspected of not being able to comply with the trial protocol.
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 | EUCTR2015-005600-28-NL |
| CCMO | NL56102.091.15 |