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TerminatedNCT05524051Updated Jul 9, 2026Results posted

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 Phase 2 interventional study of TIN816 and Placebo in Acute Kidney Injury Following Cardiac Surgery, sponsored by Novartis Pharmaceuticals. Terminated at 37 sites in 15 countries. Open to participants aged 45 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-07-09.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Why this study was terminated
Sponsor Decision
Phase
Phase 2
Study type
Interventional
Enrollment
102
Allocation
Randomized
Ages
45 Years to 100 Years
Sex
All
01

Study summary

This was 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.

Read the detailed description

The study consisted of a pre-operative period (screening visit), a treatment period (Day 1), and a post-treatment follow-up period (Day 2 to Day 90 (EOS)). Participants were followed daily in the hospital from Day 2 to Day 8 as in-patients or at home/nearby accommodation (e.g., hotel or rehabilitation unit if discharged earlier than Day 8), and then as out-patients until the end of the study (Day 30 and Day 90 (EOS) visits).

02

Conditions studied

  • Acute Kidney Injury Following Cardiac Surgery

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Keywords

  • acute kidney injury
  • cardiac surgery
03

In context

Acute Kidney Injury

1,595 studies on the registry are indexed under Acute Kidney Injury; 371 are open to participants now.

This study's enrollment of 102 is close to the median of 100 across 763 interventional studies indexed under Acute Kidney Injury.

Browse Acute Kidney Injury studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
45 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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 should be assessed in the sitting or supine position and be within the following ranges:

    1. body temperature between 35.0-37.5 °C
    2. blood pressure (systolic 100-160 mmHg, diastolic \< 100 mmHg)
    3. 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 obtained within the last 6 months 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

Exclusion criteria

Exclusion Criteria:

  • eGFR at screening \<15 mL/min/1.73 m2 (calculated using CKD-EPI 2021 equation).
  • Receiving renal replacement therapy currently or at any time within 3 months prior to screening.

  • 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
    • History of platelet dysfunction: e.g., ADP induced platelet aggregation lower than 60 %
    • History of coagulation factor deficiency: including, but not limited to fibrinogen ≤ 2.5 g/L or Von Willebrand factor (vWF) ≤ 50 IU/dL
  • 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, symptothermal and 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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
102 participants (actual)

Study arms

  • Experimental
    TIN816 2 mg/kg

    TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.

  • Experimental
    TIN816 4 mg/kg

    TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.

    Drug: TIN816

  • Placebo comparator
    Placebo

    Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.

    Other: Placebo

Interventions

  • DrugTIN816

    TIN816 was administered as a single intravenous (i.v.) infusion over 2 hours.

  • OtherPlacebo

    Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.

06

What researchers measure

Primary outcomes

  1. Ratio of the Highest Serum Creatinine Value up to and Including Study Day 6 Versus Baseline

    The log-transformed ratio of the highest serum creatinine value up to and including Study Day 6 vs baseline was analysed by a linear model. The estimated mean and 90% confidence interval of the difference in log-transformed ratios vs baseline between each TIN816 treatment group and placebo were then back-transformed to obtain the geometric mean ratio. The geometric mean ratio (GMR) represents the ratio between TIN816 and placebo geometric mean estimates for the serum creatinine Day 6 to baseline geometric mean estimates.

    Time frame: Baseline, Day 1 - Day 6

Secondary outcomes

  1. Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria

    AKI incidence over the first week after surgery (Day 1 to Day 8) was measured using the modified AKIN classification system, based on changes in serum creatinine compared to pre-operative value. Severity of AKI was assessed using three stages, with stage 1 being mild or least severe and stage 3 the most severe. Stage 1: Serum creatinine (SCr) ≥1.5 - \<2.0 x baseline within 7 days post-surgery Or ↑ SCr by ≥26.5 μmol/L (≥0.3 mg/dL) within 2 days post-surgery Stage 2: SCr ≥2.0 - \<3.0 x baseline within 7 days post-surgery Stage 3: SCr ≥3.0x baseline within 7 days post-surgery Or ↑ SCr to ≥353.6 μmol/L (4.0 mg/dL) AND by ≥44.2 μmol/L (0.5 mg/dL) within 7 days post-surgery Or Initiation of RRT within 7 days post-surgery

    Time frame: Baseline, Day 8

  2. Number of Participants With Anti-TIN816 Antibodies

    Immunogenicity (IG) serum samples were collected to evaluate production of anti-TIN816 antibodies (anti-drug antibodies, ADAs).

    Time frame: Day 1 pre-dose, Day 8, Day 30 and Day 90

  3. Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30)

    The number of participants having major adverse kidney event at Day 30 (MAKE30) was assessed using the following components: 1. death through day 30, 2. initiation of renal replacement therapy (RRT) through day 30, and 3. ≥25% reduction in eGFR from baseline to 30 days after surgery.

    Time frame: Baseline, Day 30

  4. Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90)

    The number of participants having major adverse kidney event at Day 90 (MAKE90) was assessed using the following components: 1. death through day 90, 2. initiation of renal replacement therapy (RRT) through day 90, and 3. ≥25% reduction in eGFR from baseline to 90 days after surgery.

    Time frame: Baseline, Day 90

07

Results

Posted Apr 2, 2026

Participant flow

Participants were enrolled at 36 investigative sites in 15 countries. Participants were originally randomized in a ratio of 1:1 (TIN816 2 mg/kg:placebo). After a protocol amendment participants were randomized in a ratio of 3:1 (TIN816 4 mg/kg:placebo).

Participant flow — Overall Study
MilestoneTIN816 2 mg/kgTIN816 4 mg/kgPlacebo
Started224337
Completed193732
Not completed365
Withdrew: Withdrawal by subject213
Withdrew: Death030
Withdrew: Lost to follow-up001
Withdrew: Randomized but not treated121

Outcome measures

PrimaryRatio of the Highest Serum Creatinine Value up to and Including Study Day 6 Versus Baseline

The log-transformed ratio of the highest serum creatinine value up to and including Study Day 6 vs baseline was analysed by a linear model. The estimated mean and 90% confidence interval of the difference in log-transformed ratios vs baseline between each TIN816 treatment group and placebo were then back-transformed to obtain the geometric mean ratio. The geometric mean ratio (GMR) represents the ratio between TIN816 and placebo geometric mean estimates for the serum creatinine Day 6 to baseline geometric mean estimates.

Time frame:
Baseline, Day 1 - Day 6
Reported as:
Geometric mean · ratio
Ratio of the Highest Serum Creatinine Value up to and Including Study Day 6 Versus Baseline
ratioTIN816 2 mg/kgTIN816 4 mg/kgPlacebo
Ratio of the Highest Serum Creatinine Value up to and Including Study Day 6 Versus Baseline1.215 (1.07 to 1.38)1.318 (1.18 to 1.48)1.226 (1.08 to 1.39)
Statistical analysis
  • TIN816 2 mg/kg vs Placebo · ANCOVA · p = 0.4543 (p-value is 1-sided) · Geometric mean ratio: 0.991 · 90% CI 0.87 to 1.13
  • TIN816 4 mg/kg vs Placebo · ANCOVA · p = 0.8667 (p-value is 1-sided) · Geometric mean ratio: 1.075 · 90% CI 0.97 to 1.20
SecondaryNumber of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria

AKI incidence over the first week after surgery (Day 1 to Day 8) was measured using the modified AKIN classification system, based on changes in serum creatinine compared to pre-operative value. Severity of AKI was assessed using three stages, with stage 1 being mild or least severe and stage 3 the most severe. Stage 1: Serum creatinine (SCr) ≥1.5 - \<2.0 x baseline within 7 days post-surgery Or ↑ SCr by ≥26.5 μmol/L (≥0.3 mg/dL) within 2 days post-surgery Stage 2: SCr ≥2.0 - \<3.0 x baseline within 7 days post-surgery Stage 3: SCr ≥3.0x baseline within 7 days post-surgery Or ↑ SCr to ≥353.6 μmol/L (4.0 mg/dL) AND by ≥44.2 μmol/L (0.5 mg/dL) within 7 days post-surgery Or Initiation of RRT within 7 days post-surgery

Time frame:
Baseline, Day 8
Reported as:
Count of participants · Participants
Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria
ParticipantsTIN816 2 mg/kgTIN816 4 mg/kgPlacebo
No AKI131624
Stage 161810
Stage 2111
Stage 3161
SecondaryNumber of Participants With Anti-TIN816 Antibodies

Immunogenicity (IG) serum samples were collected to evaluate production of anti-TIN816 antibodies (anti-drug antibodies, ADAs).

Time frame:
Day 1 pre-dose, Day 8, Day 30 and Day 90
Reported as:
Count of participants · Participants
Number of Participants With Anti-TIN816 Antibodies
ParticipantsTIN816 2 mg/kgTIN816 4 mg/kgPlacebo
Day 1 pre-dose - positive000
Day 8 - positive000
Day 30 - positive000
Day 90 - positive000
SecondaryNumber of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30)

The number of participants having major adverse kidney event at Day 30 (MAKE30) was assessed using the following components: 1. death through day 30, 2. initiation of renal replacement therapy (RRT) through day 30, and 3. ≥25% reduction in eGFR from baseline to 30 days after surgery.

Time frame:
Baseline, Day 30
Reported as:
Count of participants · Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30)
ParticipantsTIN816 2 mg/kgTIN816 4 mg/kgPlacebo
Participants with any MAKE304116
Death through day 30030
Initiation of renal replacement therapy to day 30031
≥25% eGFR reduction from baseline to day 30465
SecondaryNumber of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90)

The number of participants having major adverse kidney event at Day 90 (MAKE90) was assessed using the following components: 1. death through day 90, 2. initiation of renal replacement therapy (RRT) through day 90, and 3. ≥25% reduction in eGFR from baseline to 90 days after surgery.

Time frame:
Baseline, Day 90
Reported as:
Count of participants · Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90)
ParticipantsTIN816 2 mg/kgTIN816 4 mg/kgPlacebo
Participants with any MAKE902102
Death through day 90030
Initiation of renal replacement therapy to day 90031
≥25% eGFR reduction from baseline to day 90251

Adverse events

Collected over Adverse events were reported up to approximately 90 days after administration of study drug.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TIN816 2 mg/kg0/21 (0%)6/21 (28.6%)17/21 (81%)
TIN816 4 mg/kg3/41 (7.3%)16/41 (39%)30/41 (73.2%)
Placebo0/36 (0%)9/36 (25%)26/36 (72.2%)
Total3/98 (3.1%)31/98 (31.6%)73/98 (74.5%)
Most frequent serious events
Showing 10 of 47
Most frequent serious events
EventTIN816 2 mg/kgTIN816 4 mg/kgPlaceboTotal
Cardiac failureCardiac disorders3/212/410/365/98
CoagulopathyBlood and lymphatic system disorders1/211/413/365/98
Atrioventricular block completeCardiac disorders0/210/413/363/98
Acute kidney injuryRenal and urinary disorders0/213/410/363/98
SyncopeNervous system disorders0/210/412/362/98
Atrial fibrillationCardiac disorders0/212/410/362/98
PneumoniaInfections and infestations0/212/410/362/98
Cardiac tamponadeCardiac disorders1/210/411/362/98
Pericardial effusionCardiac disorders1/210/410/361/98
Ventricular tachycardiaCardiac disorders1/210/410/361/98
Most frequent other events
Showing 10 of 38
Most frequent other events
EventTIN816 2 mg/kgTIN816 4 mg/kgPlaceboTotal
Acute kidney injuryRenal and urinary disorders3/2116/419/3628/98
Atrial fibrillationCardiac disorders6/2114/415/3625/98
AnaemiaBlood and lymphatic system disorders5/2111/418/3624/98
Urinary tract infectionInfections and infestations3/212/410/365/98
DeliriumPsychiatric disorders3/212/413/368/98
HypotensionVascular disorders2/215/415/3612/98
LeukocytosisBlood and lymphatic system disorders1/215/411/367/98
ConstipationGastrointestinal disorders0/213/414/367/98
HypervolaemiaMetabolism and nutrition disorders1/214/414/369/98
ThrombocytopeniaBlood and lymphatic system disorders2/214/413/369/98

Baseline characteristics

Randomized and treated participants

Age, Continuous
Age, Continuous(years)TIN816 2 mg/kgTIN816 4 mg/kgPlaceboTotal
Mean70.7 ± 7.9970.3 ± 8.0171.9 ± 6.8571.0 ± 7.56
Sex: Female, Male
Sex: Female, Male(Participants)TIN816 2 mg/kgTIN816 4 mg/kgPlaceboTotal
Female108927
Male11332771
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)TIN816 2 mg/kgTIN816 4 mg/kgPlaceboTotal
Black or African American0112
Asian38516
White17211553
Unknown0101
Not Reported1101526
08

Study locations

37 sites
  • Mayo Clinic Phoenix
    Phoenix, Arizona 85054, United States
  • Duke Univ Medical Center
    Durham, North Carolina 27710, United States
  • Novartis Investigative Site
    CABA, Buenos Aires C1118AAT, Argentina
  • Novartis Investigative Site
    Buenos Aires, C1428DCO, Argentina
  • Novartis Investigative Site
    CABA, C1181ACH, Argentina
  • Novartis Investigative Site
    Genk, Limburg 3600, Belgium
  • Novartis Investigative Site
    Leuven, 3000, Belgium
  • Novartis Investigative Site
    Salvador, Estado de Bahia 40323-010, Brazil
  • Novartis Investigative Site
    São Paulo, São Paulo 05403 000, Brazil
  • Novartis Investigative Site
    Montreal, Quebec H1T 1C8, Canada
  • Novartis Investigative Site
    Montreal, Quebec H2X 0A9, Canada
  • Novartis Investigative Site
    Montreal, Quebec H4J 1C5, Canada
  • Novartis Investigative Site
    Québec, Quebec GIV 4G5, Canada
  • Novartis Investigative Site
    Ostrava, Poruba 708 52, Czechia
  • Novartis Investigative Site
    Tartu, Estonia 50406, Estonia
  • Novartis Investigative Site
    Nantes, 44093, France
  • Novartis Investigative Site
    Neuilly-sur-Seine, 92200, France
  • Novartis Investigative Site
    Paris, 75013, France
  • Novartis Investigative Site
    Poitiers, 86021, France
  • Novartis Investigative Site
    Rennes, 35033, France
  • Novartis Investigative Site
    Regensburg, Bavaria 93053, Germany
  • Novartis Investigative Site
    Dresden, Saxony 01307, Germany
  • Novartis Investigative Site
    Leipzig, Saxony 04289, Germany
  • Novartis Investigative Site
    Essen, 45147, Germany
  • Novartis Investigative Site
    Pécs, Baranya 7623, Hungary
  • Novartis Investigative Site
    Debrecen, Hajdu Bihar Megye 4032, Hungary
  • Novartis Investigative Site
    Budapest, H 1096, Hungary
  • Novartis Investigative Site
    Budapest, H-1083, Hungary
  • Novartis Investigative Site
    Ahmedabad, Gujarat 380054, India
  • Novartis Investigative Site
    Lucknow, Uttar Pradesh 226003, India
  • Novartis Investigative Site
    Vilnius, LT-08406, Lithuania
  • Novartis Investigative Site
    Singapore, 119074, Singapore
  • Novartis Investigative Site
    Santiago Compostela, A Coruna 15706, Spain
  • Novartis Investigative Site
    Badalona, Barcelona 08916, Spain
  • Novartis Investigative Site
    Barcelona, Catalonia 08907, Spain
  • Novartis Investigative Site
    Madrid, 28006, Spain
  • Novartis Investigative Site
    Taipei, 10002, Taiwan
09

References and documents

Study documents

  • Study protocol · Jan 25, 2024
  • Statistical analysis plan · Jul 15, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 9, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05524051
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Sep 1, 2022
Start date
Mar 3, 2023
Primary completion
Mar 26, 2025
Completion
Jun 23, 2025
Results posted
Apr 2, 2026
Last update
Jul 9, 2026

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticasl

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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