LSALT Peptide for Acute Kidney Injury During Cardiac Surgery

Recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called LSALT Peptide (also known as Metablok) to determine if it can prevent acute kidney injury (AKI) after heart surgery involving a heart-lung machine. AKI can occur when kidneys function poorly after surgery, and this trial aims to assess if this new treatment can help. Individuals scheduled for heart surgery with a heart-lung machine and who have certain kidney risk factors, such as diabetes or high blood pressure, might be suitable candidates for this trial. Participants will receive either the LSALT Peptide or a placebo (a substance with no active drug) to compare results. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that LSALT Peptide is likely to be safe for humans?

Research has shown that LSALT peptide, the treatment being tested, has undergone safety studies. Previous patients generally tolerated the peptide well. In earlier studies, researchers reported no major safety issues. The treatment was tested for its ability to reduce organ inflammation and showed promise.

Although LSALT peptide remains in a mid-stage trial, with more data being collected, current evidence suggests it is safe for humans. Importantly, trials so far have reported no major negative side effects. This should provide some confidence about its safety as more people join the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute kidney injury?

Researchers are excited about LSALT Peptide for acute kidney injury during cardiac surgery because it targets inflammation in the kidneys, a crucial factor in preventing damage. Unlike standard treatments that mainly focus on managing symptoms and supporting kidney function, LSALT Peptide works by inhibiting a protein that contributes to inflammation and tissue injury. This new mechanism of action holds promise for reducing the risk of kidney injury more effectively and rapidly than current options.

What evidence suggests that LSALT Peptide might be an effective treatment for acute kidney injury?

Research has shown that LSALT peptide, which participants in this trial may receive, might help treat sudden kidney problems during heart surgery. In animal studies, LSALT peptide reduced kidney damage and swelling caused by poor blood flow. This is important because kidney issues often occur when the kidneys don't receive enough blood during surgery. LSALT peptide blocks a protein called DPEP1, which is involved in organ swelling. Previous studies have demonstrated that targeting DPEP1 can protect organs from damage. These findings suggest LSALT peptide may help prevent or reduce kidney problems in patients undergoing heart surgery. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05879432

LSALT Peptide for Prevention or Attenuation of Acute ...

This study is a randomized, double-blind, multicenter interventional study to assess safety and efficacy of LSALT peptide versus placebo (matching drug-free ...

2.

archbiopartners.com

archbiopartners.com/our-science/lsaltpeptide/

Targeting acute kidney injury with LSALT peptide

The data from that trial provided the first-ever evidence validating Dipeptidase-1 (DPEP1) as a mediator of organ inflammation and therapeutic target in humans.

3.

withpower.com

withpower.com/trial/phase-2-acute-kidney-injury-6-2023-80d00

LSALT Peptide for Acute Kidney Injury During Cardiac ...

In mouse models, treatment with ELA32 or ELA11 significantly reduced renal fibrosis, inflammation, and dysfunction caused by ischemia-reperfusion injury, while ...

4.

firstwordpharma.com

firstwordpharma.com/story/5986898

Arch Biopartners Announces First Patient Successfully ...

The volunteer patient completed five days of dosing as part of the Company's ongoing Phase II trial evaluating LSALT peptide to prevent and ...

5.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/arch-phase-ii-cs-aki/

Arch Biopartners doses first subject in trial of acute kidney ...

Arch Biopartners has dosed the first patient in Canada in its Phase II clinical trial of LSALT peptide (Metablok) for acute kidney injury.