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A study, with chance selection of treatment unknown to the patients and doctors, to test theUlaritide as treatment for Acute Kidney Ingury in patients post cardiac surgery

Phase 1
Active, not recruiting
Conditions
Acute kidney injury in patients post cardiac surgery
MedDRA version: 21.1Level: PTClassification code 10069339Term: Acute kidney injurySystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Registration Number
EUCTR2018-004871-11-DE
Lead Sponsor
Cardiorentis AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
45
Inclusion Criteria

1. Male and post-menopausal female patients of = 18 years. Post-menopause is defined as = 12 months after the last menstruation without an alternative medical cause
2. Body mass index = 35 kg/m2
3. Decrease of post-surgery GFR-1h-Crea measured twice approximately 1 hour apart within the first 3 hours post-surgery =50% compared to pre-surgery eGFR (CKD-EPI)
4. Index hospitalization for planned cardiac surgery via open sternotomy on cardiopulmonary bypass namely coronary artery bypass graft, valve surgery, thoracic aortic surgery, repair of ventricular septal defect or a combination thereof
5. Preoperative predictive score for cardiac surgery-associated AKI of 3 or higher according to Jiang et al., 201615
6. Hemodynamic stability defined as:
a. Systolic blood pressure (SBP) >90 mmHg in at least two consecutive non-invasive measurements that are at least 60 minutes apart in a 2-hour time window immediately post-surgery
b. No increase in vasopressor and/or inotropic support at the end of a 2-hour time window immediately post-surgery compared to its start
7. Signed written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Documented medical history of renal artery stenosis (=70%), nephrotic syndrome, renal sclerosis
2. Clinical diagnosis of
a. Severe cardiogenic shock (INTERMACS level I) or extracorporal membrane oxygenation, or any other short-term pre-surgery mechanical circulatory support other than intra-aortal balloon pump
b. Right ventricular infarction
3. Body temperature >38.0°C on the day before surgery
4. Patients started on dialysis prior to surgery or immediately thereafter
5. Pre-surgery eGFR (CKD-EPI) <60 mL/min/1.73 m2 based on serum concentrations of creatinine and cystatin C
6. Treatment with sacubitril-valsartan from the day before surgery until 60 hours post infusion start
7. Advanced cancer or any other acute or chronic consuming disease which could relevantly interfere with the surgery outcome (survival) or success of test treatments
8. Known hypersensitivity to the active substance or to any of the excipients of each investigational medicinal product (verum and placebo) or other natriuretic peptides
9. Known Hepatitis B or C or HIV infection
10. Participation in an interventional clinical drug trial within 1 month prior to randomization
11. Legal incapacity or limited legal capacity
12. Breastfeeding or pregnancy
13. Employees of the sponsor or patients who are employees or relatives of the investigator
14. Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Part A:<br>• To investigate the safety, tolerability and dose-effect-relationship of 3 different doses of ularitide on renal and central hemodynamics and on renal excretory function in patients post cardiac surgery, who have developed AKI (as defined in this protocol), and to identify the individual maximum tolerated dose of ularitide in these patients.<br>Part B:<br>• To investigate the safety, tolerability, and effect of the individual maximum tolerated ularitide dose identified in Part A for up to an additional 42 hours.;Secondary Objective: Not applicable;Primary end point(s): Change (absolute and percentage) of glomerular filtration rate based on 1-hour creatinine clearance (GFR-1h-Crea) at the end of the dose escalation phase (6 hours post infusion start) versus (vs) Baseline (mean value from 2 post-surgery screening measurements);Timepoint(s) of evaluation of this end point: 6 hours post infusion start
Secondary Outcome Measures
NameTimeMethod
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