LSALT Peptide for Acute Kidney Injury During Cardiac Surgery

Recruiting at 8 trial locations

Overseen By David Luke

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Arch Biopartners Inc.

Disqualifiers: Severe CKD, Active cancer, Sepsis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 5 days

240 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug LSALT Peptide for treating acute kidney injury during cardiac surgery?

Research on similar peptides, like Elabela, shows they can protect against kidney injury by reducing inflammation and cell damage in animal models. This suggests that LSALT Peptide might also help protect the kidneys during cardiac surgery. ^{1 2 3 4 5}

What makes LSALT Peptide unique for treating acute kidney injury during cardiac surgery?

LSALT Peptide is unique because it targets inflammation and tissue damage specifically during cardiac surgery, which is a common cause of acute kidney injury (AKI). Unlike other treatments, it may offer a novel approach by focusing on reducing inflammation and protecting kidney tissues during the surgical process. ^{1 2 5 6 7}

What is the purpose of this trial?

To evaluate the percentage of subjects with AKI within 7 days following on-pump cardiac surgery defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria: 1. Increase in baseline (pre-surgery) serum creatinine (SCr) by ≥26.5 μmol/L (≥0.3 mg/dL) within 7 days; OR 2. Increase in baseline SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the first 7 days following surgery; OR 3. Urine output \< 0.5 mL/kg/h for \>6 hours.

Eligibility Criteria

This trial is for adults over 18 who are undergoing on-pump cardiac surgery, such as bypass grafts or valve replacements. It's specifically for those with moderate chronic kidney disease (CKD Stage 3) and additional risk factors like diabetes or reduced heart function, or simply being aged 75 years or older.

Inclusion Criteria

Have the following AKI risk factors: CKD Stage 3 (CKD-EPI eGFR ≥ 30 and < 60 mL/min/1.73 m2) and ONE of the following additional risk factors (below; excluding age ≥ 75 years) OR CKD Stage 2 (CKD-EPI eGFR ≥ 60 and < 90 mL/min/1.73 m2) and TWO of the following additional risk factors: Age ≥ 75 years, Combined valve & coronary artery surgery, Left ventricular ejection fraction (LVEF) ≤ 35% by invasive or noninvasive techniques, Diabetes mellitus on treatment, Albuminuria (random urine albumin:creatinine ratio >30 mg/mmol), Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control throughout the study and for at least 1 day following the end of study and have a negative urine pregnancy test at the Screening visit. A WCBP is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months, surgical sterilization, or the implant. In patients who are not sexually active, abstinence is an acceptable form of birth control and urine will be tested per protocol. Women who are of nonchild-bearing potential, i.e., post-menopause, must have this condition captured in their medical history. Pregnant women and nursing mothers are excluded from this study. Patient or Legally Authorized Representative (LAR) is available and willing to give written informed consent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures

I am scheduled for heart surgery that includes using a heart-lung machine.

Exclusion Criteria

I currently have acute kidney injury.

I might have an infection in my blood.

Pregnancy or lactation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive LSALT peptide or placebo intravenously twice daily for 5 days

5 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including kidney function assessments

28 days

Regular monitoring (in-person)

Treatment Details

Interventions

• LSALT Peptide

Trial Overview The study tests if LSALT Peptide can prevent or lessen acute kidney injury after heart surgery compared to a placebo. The main measure is changes in serum creatinine levels or urine output according to the KDIGO criteria within the first week after surgery.

Participant Groups

Group I: LSALT Peptide Experimental Treatment 1 Intervention

LSALT peptide 10 mg IV administered over 1 hour twice daily, every 12 ± 1 hour, for 5 days

Group II: Placebo Placebo Group 1 Intervention

Placebo IV administered over 1 hour twice daily, every 12 ± 1 hour, for 5 days

Who Is Running the Clinical Trial?

Arch Biopartners Inc.

Lead Sponsor

Trials

4

Recruited

3,300+

Findings from Research

ELABELA (ELA) and its fragments, ELA32 and ELA11, show protective effects against renal ischemia-reperfusion injury by reducing DNA damage, inflammation, and apoptosis in kidney cells, indicating their potential as therapeutic candidates for acute kidney injury (AKI).

In mouse models, treatment with ELA32 or ELA11 significantly reduced renal fibrosis, inflammation, and dysfunction caused by ischemia-reperfusion injury, while a mutant form of ELA11 did not provide the same protective effects, highlighting the importance of the peptide's structure for its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ELABELA and an ELABELA Fragment Protect against AKI. Chen, H., Wang, L., Wang, W., et al.[2018]

The Fc-ELA fusion protein showed significant renoprotective effects in mice with endotoxemia-induced acute kidney injury (AKI), improving kidney function and reducing inflammation after LPS treatment.

Treatment with Fc-ELA restored the expression of the kidney peptide hormone apela and reduced reactive oxygen species (ROS) production, indicating its potential as a therapeutic option for AKI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-Elabela fusion protein attenuates lipopolysaccharide-induced kidney injury in mice. Xu, F., Zhou, H., Wu, M., et al.[2020]

In a mouse model, the cyclic helical B-peptide (CHBP) significantly improved kidney function and reduced tissue damage caused by aristolochic acid (AA), as evidenced by decreased blood urea nitrogen and serum creatinine levels.

CHBP demonstrated its protective effects by reducing apoptosis and inflammation in the kidneys, likely through the inhibition of caspase-3 activation and the enhancement of anti-apoptotic proteins like bcl-2 and bcl-xl.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effects of cyclic helix B peptide on aristolochic acid induced acute kidney injury. Zeng, Y., Zheng, L., Yang, Z., et al.[2018]

Infusing synthetic human atrial natriuretic peptide (ANP) in the immediate postoperative period after coronary bypass surgery significantly increased urine flow, inulin clearance, and sodium and osmole clearance in 30 patients with normal kidney function.

ANP infusion did not affect mean arterial pressure or heart rate, suggesting it is safe for renal function enhancement without compromising hemodynamics during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of human atrial natriuretic peptide in patients after coronary artery bypass surgery. Bergman, A., Odar-Cederlöf, I., Westman, L., et al.[2019]

The cyclic helix B peptide (CHBP) significantly improved kidney function after preservation and reperfusion, as shown by increased renal blood flow, oxygen consumption, and urine output, while also reducing tissue damage and serum potassium levels in a study involving 5 porcine kidneys.

CHBP appears to protect against renal ischemia-reperfusion injury by decreasing apoptosis and inflammation, as indicated by lower levels of caspase-3 and myeloperoxidase+ cells, while increasing the expression of heat shock protein 70 (HSP70), suggesting a potential new method for preserving donor kidneys before transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate Ameliorates Ischemia-Reperfusion Injury in Isolated Porcine Kidneys. Yang, C., Hosgood, SA., Meeta, P., et al.[2020]

In a study using an ovine model, researchers identified 20 candidate protein biomarkers associated with acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF), which could help in early detection and treatment.

Among these biomarkers, 6 were previously known, while 14 were novel, indicating potential new avenues for understanding kidney injury mechanisms and improving patient outcomes in ADHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure. Templeton, EM., Lassé, M., Kleffmann, T., et al.[2022]

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication that can significantly increase the risk of complications and death after surgery.

Identifying and minimizing risk factors for CSA-AKI can lead to better postoperative outcomes, reducing both morbidity and mortality rates in cardiac surgery patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review. Harky, A., Joshi, M., Gupta, S., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

ELABELA and an ELABELA Fragment Protect against AKI. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Fc-Elabela fusion protein attenuates lipopolysaccharide-induced kidney injury in mice. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Protective effects of cyclic helix B peptide on aristolochic acid induced acute kidney injury. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of human atrial natriuretic peptide in patients after coronary artery bypass surgery. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate Ameliorates Ischemia-Reperfusion Injury in Isolated Porcine Kidneys. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure. [2022]

7. Brazil pubmed.ncbi.nlm.nih.gov

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review. [2020]