Ravulizumab for Kidney Damage from Heart Surgery

(ARTEMIS Trial)

Not currently recruiting at 188 trial locations

Overseen By Katherine Wang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Must not be taking: Complement inhibitors

Disqualifiers: Transplantation, Cardiogenic shock, Active infection, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ravulizumab to determine if it can reduce kidney damage after heart surgery. It targets individuals with chronic kidney disease (CKD) undergoing planned heart operations involving cardiopulmonary bypass (CPB). Participants will receive either ravulizumab or a placebo through an IV before surgery. Ideal candidates have known CKD and are scheduled for specific heart surgeries, such as valve replacements or multi-vessel bypass. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you have used complement inhibitors or had plasmapheresis or plasma exchange in the past year, or if you plan to use them during the study.

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

Research has shown that ravulizumab is generally safe for patients. In studies where it treated conditions like paroxysmal nocturnal hemoglobinuria (PNH), patients received it safely over long periods. For instance, a study with 244 patients over more than five years found its safety acceptable.

Some participants experienced side effects, but these were uncommon. While ravulizumab is approved for other uses, its safety for reducing kidney damage after heart surgery remains under investigation. The current phase of the trial suggests that past studies support its safety, but more information is needed to confirm its use for this specific purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for kidney damage from heart surgery, which often involve supportive care and medications to manage symptoms, Ravulizumab acts by inhibiting the complement system, a part of the immune response that can cause inflammation and damage. Researchers are excited about Ravulizumab because it targets a specific pathway involved in kidney injury, potentially reducing damage right at the source. This targeted action could lead to better protection and recovery of kidney function compared to existing therapies, which mainly focus on mitigating symptoms rather than addressing the underlying cause.

What evidence suggests that ravulizumab might be an effective treatment for kidney damage from heart surgery?

Research shows that ravulizumab, which participants in this trial may receive, might help protect the kidneys of patients undergoing heart surgery. In earlier studies, patients who received ravulizumab before surgery had a lower risk of serious kidney problems compared to those who received a placebo. Ravulizumab blocks a part of the immune system that can cause inflammation and kidney damage. This treatment has already shown promise in protecting kidney function in other conditions, suggesting it may work well here too. Evidence indicates that just one dose could significantly benefit those at risk. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with chronic kidney disease (CKD stages 3A, 3B, or 4) who weigh at least 30 kg and are scheduled for non-emergency heart surgery using cardiopulmonary bypass. Candidates should not have used certain kidney treatments or had infections recently and must be willing to get vaccinated against N meningitidis if needed.

Inclusion Criteria

I weigh at least 30 kilograms.

I have been diagnosed with moderate to severe kidney disease for at least 3 months.

I am scheduled for heart surgery that may include bypass or valve repair.

Exclusion Criteria

I have not used kidney replacement therapy or had acute kidney injury in the last 30 days.

I haven't used complement inhibitors or undergone plasmapheresis in the last year.

I am scheduled for a single-vessel bypass surgery without any valve procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single weight-based dose of ravulizumab or placebo via intravenous infusion, 1 to 7 days prior to surgery

1 week

Surgery

Participants undergo non-emergent cardiac surgery with CPB

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on the clinical consequences of AKI (MAKE) at 90 days

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Ravulizumab

Trial Overview The ARTEMIS study is testing whether a single dose of ravulizumab given intravenously can reduce the risk of acute kidney injury after heart surgery compared to a placebo. The focus is on seeing if this treatment helps avoid major adverse kidney events within 90 days post-surgery.

How Is the Trial Designed?

Group I: Ravulizumab Experimental Treatment 1 Intervention

Participants will receive a single weight-based dose of ravulizumab, via intravenous infusion, 1 to 7 days prior to surgery.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive a single weight-based dose of placebo via intravenous infusion, 1 to 7 days prior to surgery.

Ravulizumab is already approved in United States, European Union for the following indications:

Approved in United States as Ultomiris for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Atypical hemolytic uremic syndrome (aHUS)

Approved in European Union as Ultomiris for:

• Paroxysmal nocturnal haemoglobinuria (PNH)

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Published Research Related to This Trial

In a study of 36 kidney transplant patients with atypical hemolytic uremic syndrome (aHUS), prophylactic treatment with eculizumab (ECU) effectively prevented recurrence in high-risk patients, demonstrating its efficacy even with grafts from suboptimal donors.

Patients with early de novo aHUS showed a better response to ECU compared to those with late onset, indicating that earlier diagnosis and treatment are crucial for better outcomes, and ECU was well tolerated across all cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics, management and outcomes of atypical haemolytic uraemic syndrome in kidney transplant patients: a retrospective national study. Portoles, J., Huerta, A., Arjona, E., et al.[2022]

In a study of 58,399 adult patients undergoing open cardiac surgery, those with preoperative statin exposure had a significantly lower prevalence of postoperative acute kidney injury (CSA-AKI), with rates of 30.7% compared to 36.3% in those without statins.

Preoperative statin use was found to be a protective factor against severe cases of CSA-AKI (stage 3), showing a reduced risk with an odds ratio of 0.671, indicating that statins may help safeguard kidney function during and after cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Preoperative Statin Exposure and Acute Kidney Injury in Adult Patients Undergoing Cardiac Surgery. Tian, Y., Li, X., Wang, Y., et al.[2022]

Acute kidney injury (AKI) occurred in 6.7% of patients after cardiac surgery with extracorporeal circulation, highlighting a significant risk associated with this procedure.

Key independent risk factors for developing AKI included preoperative serum creatinine levels, ejection fraction, and intraoperative cardiopulmonary bypass time, suggesting that careful preoperative assessment and monitoring could help prevent AKI in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Risk factors for acute kidney injury following 5100 cardiac surgeries with extracorporeal circulation]. Ling, LG., Zeng, N., Liu, J., et al.[2009]

In a study analyzing 98,953 records from adult patients undergoing cardiopulmonary bypass, the use of zero-balance ultrafiltration (ZBUF) was associated with a significant 16.1% reduction in intraoperative urine output compared to patients not using ZBUF.

The findings suggest that ZBUF may negatively impact renal function during surgery, as each liter of ZBUF volume correlated with a decrease in urine output, indicating a need for further research to explore these effects in prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zero-Balance Ultrafiltration during Cardiopulmonary Bypass Is Associated with Decreased Urine Output. Stammers, AH., Tesdahl, EA., Mongero, LB., et al.[2021]

Ravulizumab is a monoclonal antibody that inhibits complement C5, effectively preventing cell lysis in conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), and received its first approval in the USA in December 2018 for treating adults with PNH.

The drug has been developed using technology to extend its half-life, allowing for less frequent dosing, and is currently being evaluated for additional uses in myasthenia gravis and IgA nephropathy, as well as a subcutaneous formulation for easier administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: First Global Approval. McKeage, K.[2020]

Eculizumab, an anti-C5 monoclonal antibody, has shown effectiveness in treating acute antibody-mediated rejection (AMR) in kidney transplant patients, but there are cases where it has failed, particularly in C4d-negative or C1q-negative AMR.

Two cases of AMR resistant to eculizumab were reported, indicating that these specific types of AMR may involve complement-independent mechanisms, suggesting a need for alternative treatments in such scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts. Burbach, M., Suberbielle, C., Brochériou, I., et al.[2022]

In a study of 1638 chronic kidney disease (CKD) patients undergoing cardiac surgery, the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI) was found to be high at 50.55%, significantly impacting both renal function and overall prognosis.

Key risk factors for developing CSA-AKI included male gender, preoperative hypertension, low hemoglobin levels, and prolonged aortic clamping time, while factors like preoperative diabetes and AKI severity affected the recovery of renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors and Prognosis of Acute Kidney Injury after Cardiac Surgery in Patients with Chronic Kidney Disease. Zhang, D., Teng, J., Luo, Z., et al.[2023]

Perioperative acute kidney injury (AKI) significantly increases the risk of complications and mortality in surgical patients, highlighting the importance of monitoring kidney function during this period.

Factors such as patient comorbidities, the urgency of surgery, and the use of nephrotoxic medications contribute to the risk of AKI, suggesting that careful management and mitigation strategies are essential to protect kidney health before, during, and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stratification and Risk Reduction of Perioperative Acute Kidney Injury: An Update. Cole, SP.[2019]

Ravulizumab is an effective treatment for atypical hemolytic uremic syndrome (aHUS), resolving thrombotic microangiopathy in 54% of adult and 78% of pediatric treatment-naïve patients within 26 weeks, making it a promising option for both groups.

With a maintenance dosage of once every 4-8 weeks, ravulizumab offers a more convenient treatment schedule compared to its predecessor eculizumab, which requires dosing every 2-3 weeks, while maintaining a good safety profile with common side effects like headache and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. Syed, YY.[2022]

In a study of 26 patients with atypical hemolytic uremic syndrome (aHUS) who underwent kidney transplantation, those receiving Eculizumab prophylaxis had a 0% relapse rate, compared to higher rates in untreated patients and those receiving plasma exchange.

The study suggests that Eculizumab is an effective preventive treatment for aHUS recurrence in kidney transplant patients, with tailored dosing based on complement pathway activity, supporting its use in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kidney transplant in patients with atypical hemolytic uremic syndrome in the anti-C5 era: single-center experience with tailored Eculizumab. Ardissino, G., Cresseri, D., Tel, F., et al.[2022]

Citations

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A phase 3 study of ravulizumab to protect patients with chronic ... This is a phase 3, randomized, double-blind, placebo-controlled, global study assessing the efficacy and safety of a single preoperative dose of ravulizumab.

2. heartlungcirc.org heartlungcirc.org/article/S1443-9506(25)00103-9/fulltext

A Phase 3 Study of Ravulizumab to Protect Patients With ... This study aims to assess whether terminal complement inhibition with ravulizumab is safe and effective in reducing MAKE and improving outcomes in patients ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40448185/

A phase 3 study of ravulizumab to protect patients with ... This is a phase 3, randomized, double-blind, placebo-controlled, global study assessing the efficacy and safety of a single preoperative dose of ravulizumab.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05746559

ARTEMIS: Ravulizumab to Protect Patients With CKD From ... A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney ...

5. artemisstudy.alexionclinicaltrials.com artemisstudy.alexionclinicaltrials.com/

ARTEMIS Study: Chronic Kidney Disease Study The purpose of the ARTEMIS Study is to evaluate the safety and efficacy of an investigational medication (ravulizumab) in reducing the risk of cardiac surgery– ...

6. ultomirishcp.com ultomirishcp.com/pnh/efficacy-and-safety/adult-data

PNH | Adult data - ULTOMIRIS® (ravulizumab-cwvz) ULTOMIRIS safety outcomes reported through the entire study period, 5.6 years in the safety population (N=244)2. Type of adverse event. Adverse reaction ...

7. astrazeneca.com astrazeneca.com/content/astraz/media-centre/medical-releases/ultomiris-ravulizumab-meaningful-survival-87-at-26-weeks-children-thrombotic-mp-after-haematopoietic-stem-cell-transplant-phase-iii-open-label-trial.html

Ultomiris (ravulizumab) demonstrated clinically meaningful ... Results showed 17.1% (7/41, 95% CI: 7.2-32.1) of participants achieved the primary endpoint of complete TMA response (a composite measure of ...