Nitric Oxide for Acute Kidney Injury

(MGHK23 Trial)

Overseen By Lorenzo Berra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Massachusetts General Hospital

Must not be taking: Oxidizing agents

Disqualifiers: Low eGFR, Hemodynamic instability, 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

Compensation: Varies

Number of Visits: 1

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether inhaled nitric oxide can treat acute kidney injury in patients undergoing certain heart surgeries. It compares nitric oxide treatment to a placebo to determine if it improves kidney function post-surgery. Suitable candidates include those undergoing elective cardiac or aortic surgery with a heart-lung machine for over 90 minutes and who have stable kidney function. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown mixed results regarding the safety of inhaled nitric oxide (iNO) in humans. Some studies suggest that iNO might increase the risk of kidney problems, particularly in patients with acute respiratory distress syndrome (ARDS). For instance, one study found a 40% higher risk of kidney issues linked to iNO, mainly in ARDS cases. Conversely, other research indicates that iNO might help prevent kidney injury in certain surgeries.

In real-world use, serious side effects like acute kidney injury and kidney failure have been reported, though they are not very common. Overall, the safety of iNO remains under study, and results are not entirely consistent.

The study's advanced phase indicates that inhaled nitric oxide has demonstrated some level of safety in earlier research. However, the current study is crucial for better understanding its safety for patients with acute kidney injury during and after surgery. ^{1 2 3 4 5}

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

Nitric oxide is unique because it offers a targeted approach to treating acute kidney injury (AKI) by utilizing inhaled nitric oxide (iNO) to improve blood flow and reduce inflammation. Unlike standard treatments that typically focus on managing symptoms and supporting kidney function, iNO directly targets the underlying issues that can cause kidney damage. Researchers are excited about iNO because it has the potential to protect the kidneys during and after surgery, especially when administered through a cardiopulmonary bypass machine, which is a novel delivery method. This targeted approach could lead to more effective prevention of AKI, which is a significant concern during surgical procedures.

What evidence suggests that nitric oxide might be an effective treatment for acute kidney injury?

Studies have shown that inhaled nitric oxide (iNO), which participants in this trial may receive, can help reduce the risk of acute kidney injury (AKI) in patients undergoing heart surgery. Some research suggests that nitric oxide gas is the first drug treatment to lower the chances of developing AKI and improve long-term kidney health. In one study, patients who received nitric oxide during surgery experienced fewer cases of AKI compared to those who did not. While some results differ, many findings support the idea that nitric oxide might protect the kidneys during surgery. Overall, the evidence suggests that nitric oxide could be effective for this condition. ^{2 3 6 7 8}

Who Is on the Research Team?

Lorenzo Berra, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for cardiac surgery patients with stable kidney function and signs of endothelial dysfunction, who will undergo a long cardiopulmonary bypass. They must not have severe kidney issues, unstable blood pressure, significant heart failure, recent blood transfusions or contrast infusions, or conditions causing hemolysis.

Inclusion Criteria

Provide written informed consent

Elective cardiac or aortic surgery with CPB>90 minutes

Stable pre-operative renal function without evidence of plasma creatinine level increase of ≥ 0.3 mg/dL over the prior 3 months and without renal replacement therapy (RRT)

Exclusion Criteria

eGFR less than 30 ml/min/1.73 m2

Emergent cardiac surgery

Life expectancy < 1 year at the time of enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive inhaled nitric oxide or placebo during and after cardiopulmonary bypass for 24 hours

24 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including daily plasma creatinine measurements until day 7 or discharge

7 days

Daily monitoring

Long-term Follow-up

Follow-up assessments at 6 weeks, 90 days, and 1 year after surgery to evaluate outcomes such as renal function, mortality, and quality of life

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Nitric Oxide
• Placebo

Trial Overview The study tests if nitric oxide can treat acute kidney injury in these patients compared to a placebo. Participants are randomly assigned to receive either nitric oxide or an inactive substance during their surgery.

How Is the Trial Designed?

Group I: Nitric Oxide Experimental Treatment 1 Intervention

Inhaled nitric oxide (iNO) will be administered via the CPB machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the ICU. Once patients are extubated they will breathe test gas via a facemask or nasal cannula. Test gas administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, iNO will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.

Group II: Control Placebo Group 1 Intervention

Inhaled nitrogen will be administered via the cardiopulmonary bypass (CPB) machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the Intensive Care Unit (ICU). Once patients are extubated they will breathe test gas via a facemask or nasal cannula. Test gas administration will commence at the onset of CPB and last for 24 hours.

Nitric Oxide is already approved in United States for the following indications:

Approved in United States as Inomax for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Approved in United States as Noxivent for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Approved in United States as GeNOsyl for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Ichinose, Fumito, M.D., Ph.D., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Kenneth, Shelton, M.D., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Kacmarek, Robert M., Ph.D., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Sundt, Thoralf M., M.D., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Villavicencio-Theoduloz, Mauricio A., M.D., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Thompson, Boyd Taylor, M.D., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Bonventre, Joseph V., M.D., Brigham Women Hospital

Collaborator

Trials

1

Recruited

250+

Shann, Kenneth G., Massachusetts General Hospital

Collaborator

Trials

1

Recruited

250+

Zapol, Warren M., M.D.

Collaborator

Trials

1

Recruited

250+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7850389/

Inhaled nitric oxide and acute kidney injury risk There are conflicting results as to the effect of inhaled nitric oxide (iNO) therapy on the risk of acute kidney injury (AKI).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6290943/

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 ... Nitric oxide gas is the first pharmacological intervention to show a reduction in the incidence of acute kidney injury and an improvement of long-term kidney ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06622291

Perioperative Nitric Oxide Prevents Acute Kidney Injury in ... The goal of this clinical trial is to determine the effectiveness of exogenous nitric oxide therapy in reducing the occurrence of acute kidney injury in ...

4. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-017-1651-z

Inhaled nitric oxide and acute kidney injury - Critical Care Outcomes are compared directly between groups, preferably accounting for the matched nature of the data. However, propensity scoring does not ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0022522320315415

Nitric oxide delivery during cardiopulmonary bypass ... In summary, NO administration was associated with decreased incidence of AKI in our patients undergoing elective cardiac surgery. CSA-AKI, Cardiac surgery- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4384233/

Inhaled nitric oxide therapy and risk of renal dysfunction The results showed that iNO therapy was associated with a 40% increased risk of renal dysfunction and the observed effect was mainly attributed to ARDS studies ...

7. link.springer.com link.springer.com/article/10.1007/s11748-023-01971-2

Real-world safety and effectiveness of inhaled nitric oxide ... Serious ADRs reported in pediatric patients were acute kidney injury (four events), renal failure (two events), hypoxia (one event), and ...

8. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-025-08986-5

Nitric oxide for the prevention of postoperative acute kidney ... This trial will evaluate whether perioperative NO administration can reduce early AKI and improve renal and clinical outcomes in high-risk ATAAD ...