A Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.
A Randomized, Multi-centric, Placebo-controlled, Participant and Investigator-blinded Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Adult Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.
ClinicalTrials.gov Identifier: NCT05524051
Novartis Reference Number: CTIN816A12201
Last Update: Mar 16, 2023
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
This is a randomized, multi-centric, placebo-controlled, participant and investigator-blinded study to evaluate the safety, tolerability and efficacy of TIN816 in adult patients at risk for acute kidney injury following cardiac surgery.
Signed informed consent must be obtained prior to participation in the study.
Participants must be able to communicate well with the investigator and to understand and comply with the requirements of the study.
Male and female patients ≥45 years at screening.
Participants must weigh at least 50 kg and maximum 150 kg to participate in the study and must have a body mass index (BMI) below 40. BMI = Body weight (kg) / [Height (m)]2.
At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position. Sitting vital signs should be within the following ranges:
oral body temperature between 35.0-37.5 °C
blood pressure (systolic 100-160 mmHg, diastolic < 100 mmHg)
pulse rate (50-100/min) stable with or without medication(s) as per Investigator assessment.
No known increase in SCr of ≥25% at screening visit compared to a previous value not older than 6 weeks as documented by a local laboratory using standard assay methodology.
Non-emergent open chest cavity major cardiopulmonary bypass (CPB) surgery with expected CPB time ≥1 hour
eGFR at screening <15 mL/min/1.73 m2 (calculated using CKD-EPI 2021 equation).
Currently receiving renal replacement therapy.
Patients with bleeding risk at screening. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following:
History of bleeding with suspected or confirmed bleeding disorder or any other high risk for bleeding in the opinion of the investigator
Thrombocytopenia: platelet count< 100x109/L
Platelet dysfunction: e.g., ADP induced platelet aggregation lower than 60 %
Pre-existing coagulation factor deficiency: including, but not limited to fibrinogen < 2.5-2.8 g/L
Any emergency surgeries performed less than 30 days before screening, including aortic dissection, and/or major congenital heart defects.
Scheduled to undergo cardiac surgery off CPB or with hypothermic circulatory arrest.
Cardiogenic shock or hemodynamic instability within four weeks prior to surgery, requiring inotropes or vasopressors or mechanical devices such as intra-aortic balloon counter-pulsation (IABP).
Have received cardiopulmonary resuscitation (CPR) within 30 days prior to cardiac surgery.
Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations.
Patients who are post-nephrectomy
Have ongoing sepsis or history of sepsis within the past 8 weeks or untreated diagnosed infection prior to screening visit. Sepsis is defined as presence of a confirmed pathogen, along with fever or hypothermia, and hypoperfusion or hypotension.
Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and until the end of study. Highly effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.