Kidney Injury Following Open-Chest Cardiac Surgery
Conditions
Brief summary
The goal of this clinical trial is to identify the optimal dose of RMC-035 for protection of long-term renal function in adult patients undergoing cardiac surgery who are at high risk of kidney injury. It will also learn about the safety of RMC-035. The main question it aims to answer is: * Does RMC-035 protect the function of kidneys after surgery? * Is RMC-035 safe? Researchers will compare RMC-035 in high dose, RMC-035 in low dose and placebo to see if * Kidney function better for participants treated with any of the RMC-035 doses? * What medical problems do participants have when receiving RMC-035? Participants will * Receive 3 doses of RMC-035 or placebo: at the beginning of surgery, end of surgery and 24h after surgery * Have extra checkups and tests during their hospital stay * Visit the clinic at two extra occasions at 60 days and 90 days after surgery for checkups and tests
Interventions
DRUGRMC-035
Protein, a recombinant variant of A1M. Concentrate for solution for infusion.
DRUGPlacebo
Identical to RMC-035 intervention devoid of the active substance.
Sponsors
Guard Therapeutics AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* eGFR ≥30 ml/min/1.73m2 * Scheduled for non-emergent surgery of any of the following types, with use of cardiopulmonary bypass (CPB): coronary artery bypass grafting (CABG), valve surgery, ascending aorta aneurysm surgery * Risk factors for acute kidney injury are present * Participant capable of providing written informed consent * Participant agrees to study restrictions such as not to take part in another interventional study, use contraception and not donate ova or sperm
Exclusion criteria
* Any medical condition that makes the participant unsuitable * Scheduled for emergent surgeries * Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries * Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR), or off-pump surgeries or left ventricular assist device (LVAD) implantation * Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices such as intraaortic balloon pumping (IABP) within 24 hours prior to surgery * Requires any of the following within one week prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of mechanical circulatory support. * Diagnosed with AKI prior to surgery * Requires cardiopulmonary resuscitation prior to surgery * Ongoing sepsis or an untreated diagnosed clinically significant infection * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3.0 times the upper limit of normal (ULN). * Total bilirubin ≥2.0 time ULN * History of solid organ transplantation * History of renal replacement therapy * Severe allergic asthma * Chronic immunosuppressive treatment that may have an impact on kidney function * Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function * Current enrolment or past recent participation in any other clinical study involving an investigational study treatment * Previously treatment of RMC-035 * Sensitivity to any of the study interventions, or components thereof
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in eGFR at Day 90 (the two arms of RMC-035 pooled compared against placebo) | 90 days | Difference in estimated glomerular filtration rate (eGFR) at Day 90 (end of study) compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of MAKE (and each MAKE component) at Day 90 | 90 days | Occurrence of major adverse kidney events (MAKE), consisting of the following components: death, any new renal replacement therapy (RRT) after surgery, or sustained loss of kidney function, defined as a 25% or greater decline in eGFR, until Day 90. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of MAKE (and each MAKE component) at Day 60 | 60 days | Occurrence of MAKE, ie death, new any renal replacement therapy (RRT) after surgery, or sustained loss of kidney function, defined as a 25% or greater decline in eGFR, until Day 60. |
| Change from baseline in eGFR at Day 7 (the two arms of RMC-035 compared pooled and separately against placebo) | 7 days | Difference in eGFR at Day 7 compared to baseline |
| Change from baseline in eGFR at Day 60 (the two arms of RMC-035 compared pooled and separately against placebo) | 60 days | Difference in eGFR at Day 60 compared to baseline |
| Change from baseline in Cystatin C until Day 7 | 7 days | Difference in Cystatin C results at Day 7 compared to baseline |
| Occurrence of AKI | 72 hours | Occurrence of acute kidney injury (AKI), based on SCr, until Day 4 |
| Change from baseline in SCr until Day 7 | 7 days | Difference in serum creatinine results at Day 7 compared to baseline |
| Presence and titer of ADAs at Day 60 | 60 days | Presence of anti-drug antibodies (ADAs) and titer of ADAs where they occur |
| Presence and titer of ADAs at Day 90 | 90 days | Presence of anti-drug antibodies (ADAs) and titer of ADAs where they occur |
| ADA activity of neutralizing native A1M | 90 days | Characteristics of any possible ADAs with regards to neutralizing A1M activity |
| ADA isotype | 90 days | Characteristics of any possible ADAs with regards to immunoglobulin isotype |
| Stage of AKI | 72 hours | Stage of any AKI occurring until Day 4 |
| Change from baseline in eGFR at Day 90 (the two arms of RMC-035 compared separately against placebo) | 90 days | Difference in eGFR at Day 90 compared to baseline |
Countries
Canada, Czechia, Germany, Spain
Outcome results
None listed