Ketamine for Aortic Aneurysm Pain Management

(2020Ketamine Trial)

Overseen By Eric Johnson, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sam Tyagi

Must be taking: Naloxone

Disqualifiers: Schizophrenia, Hydrocephalus, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well low-dose ketamine (an anesthetic) manages pain and reduces opioid use in patients undergoing certain aortic surgeries. Ketamine may relieve pain without the side effects of stronger painkillers. Participants will receive either the standard treatment or ketamine to determine which is more effective. Suitable candidates have an upcoming aorta surgery and require naloxone during their procedure. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 ketamine is likely to be safe for humans?

Research has shown that ketamine is generally safe for treating severe pain and is approved for this use in several countries. Studies have found that ketamine can lower pain levels and reduce the need for opioids after surgery. For instance, one study found that patients who received ketamine reported less pain than those who did not.

While some safety concerns exist, careful monitoring usually manages these effectively. In past trials, patients handled ketamine without major problems. It is important to note that this study is in an early phase, meaning researchers are still learning about its safety in this specific situation. Overall, current evidence suggests that ketamine is well-tolerated and effective in reducing pain. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for aortic aneurysm pain typically involve opioids or other standard pain management strategies, which can carry significant side effects and risks of dependency. Unlike these options, ketamine is unique because it acts on the NMDA receptors in the brain, offering pain relief without the same level of respiratory depression or addictive potential. Researchers are excited about ketamine because it has the potential to manage pain effectively while minimizing these common opioid-related issues. Additionally, ketamine may provide faster and longer-lasting relief, which is particularly beneficial in the post-surgery context.

What evidence suggests that ketamine might be an effective treatment for aortic aneurysm pain management?

Research has shown that ketamine can help manage pain. Studies have found that ketamine treatment can reduce the need for opioids and improve pain levels in patients after surgery. In this trial, participants in the Sub-Dissociative Ketamine arm will receive a continuous ketamine infusion alongside standard care, which has proven effective in relieving severe pain, such as in trauma and fractures. For patients undergoing heart surgery, like the aortic aneurysm repair in this study, ketamine significantly reduced opioid use and increased comfort. Overall, ketamine's ability to reduce pain makes it a promising option for managing pain while using fewer opioids. ^{1 2 6 7 8}

Who Is on the Research Team?

Samuel Tyagi, MD

Principal Investigator

University of Kentucky

Anna Rockich, Pharm D

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for individuals scheduled for elective repair of the thoracic or thoracoabdominal aorta who need naloxone infusion for spinal protection. It's not open to those allergic to ketamine, acetaminophen, or fentanyl; diagnosed with schizophrenia; with hydrocephalus or CNS mass; incarcerated persons; or pregnant/lactating individuals.

Inclusion Criteria

I am scheduled for surgery on the main artery in my chest or belly.

I need a continuous naloxone infusion for spinal protection.

Willing to give informed consent

Exclusion Criteria

I have been diagnosed with schizophrenia.

I have had hydrocephalus or a brain tumor.

I am allergic to ketamine, acetaminophen, or fentanyl.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sub-dissociative ketamine or placebo during and for 48 hours post TEVAR procedure

48 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study aims to see if low-dose ketamine can reduce pain and lessen opioid use in patients having TEVAR procedures while on naloxone infusion. Participants will receive either saline (a placebo) or ketamine alongside standard care.

How Is the Trial Designed?

Group I: Sub-Dissociative Ketamine Experimental Treatment 1 Intervention

Participants in this group will receive standard of care as well as a continuous ketamine infusion at the induction of anesthesia and for 48 hours postoperatively.

Group II: Standard of Care Placebo Group 1 Intervention

Participants in this group will receive standard of care as well as a saline infusion during the study period.

Who Is Running the Clinical Trial?

Sam Tyagi

Lead Sponsor

Trials

1

Recruited

20+

Anna Rockich

Lead Sponsor

Trials

3

Recruited

30+

Published Research Related to This Trial

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

Alpha-ketoglutarate (AKG) significantly prevents the formation and progression of abdominal aortic aneurysms (AAA) in mouse models by reducing aneurysmal dilation and aortic rupture, indicating its potential as a therapeutic agent.

AKG works by inhibiting oxidative stress and inflammation, as evidenced by decreased inflammatory cytokines and reduced macrophage infiltration, suggesting that it regulates key signaling pathways involved in AAA development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways. Liu, J., Liu, M., Feng, J., et al.[2022]

Several medications, including statins and doxycycline, may help prevent the expansion of abdominal aortic aneurysms by targeting inflammation in the aortic wall, based on various studies.

Despite promising results from animal and observational studies, there is a lack of randomized clinical trials to firmly establish the efficacy of these treatments, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can pharmacologic agents slow abdominal aortic aneurysm growth? Samson, R.[2012]

Vitamin D deficiency in a mouse model led to larger and more rupture-prone abdominal aortic aneurysms (AAAs), with a rupture rate of 48% compared to 19% in controls, indicating a significant role in AAA development.

Administering cholecalciferol (CCF) to mice with established AAAs reduced their growth and rupture rate (8% vs. 46%), suggesting that vitamin D supplementation could be a potential therapeutic strategy, likely through its effects on genes involved in extracellular matrix remodeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model. Nsengiyumva, V., Krishna, SM., Moran, CS., et al.[2021]

In a study using apolipoprotein E-deficient mice, activation of the kinin B2 receptor (B2R) was found to promote aortic rupture in abdominal aortic aneurysm (AAA) models, linked to increased neutrophil infiltration and inflammation.

Conversely, using a B2R antagonist provided protection against aortic rupture and reduced aneurysm growth, suggesting that targeting B2R signaling could be a promising therapeutic strategy for AAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Kinin B2 Receptor Signaling Controls Aortic Dilatation and Rupture in the Angiotensin II-Infused Apolipoprotein E-Deficient Mouse. Moran, CS., Rush, CM., Dougan, T., et al.[2018]

In a study of 69 gynecological surgery patients, low dose ketamine (0.15 mg/Kg) administered preoperatively did not provide a preemptive analgesic effect, as indicated by similar pain scores at rest compared to placebo.

However, patients receiving ketamine postoperatively experienced less pain upon movement on the fifth day and required less morphine in the first 6 hours, suggesting that while preemptive use is ineffective, postoperative ketamine can still improve pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. Gilabert Morell, A., Sánchez Pérez, C.[2013]

S(+)-Ketamine, at half the dose of ketamine racemate, provides similar analgesic effects while causing fewer adverse effects on cognitive functions and a smaller increase in heart rate, making it a promising option for emergency medicine.

In a study involving 16 healthy volunteers, S(+)-ketamine resulted in significantly less anterograde amnesia compared to ketamine racemate, suggesting it may be safer for use in situations where maintaining cognitive function is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. Pfenninger, E., Baier, C., Claus, S., et al.[2013]

Currently, there is no effective medical therapy available to prevent the progression of aortic aneurysm (AA), despite various pharmacological agents like β-blockers and angiotensin inhibitors being investigated.

The review highlights the gap between successful preclinical studies and clinical failures, emphasizing the need for better understanding of AA's pathophysiology to identify new therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Pharmacological Management of Aortic Aneurysm. Xiang, B., Zhu, S., Li, J., et al.[2022]

In a study of 417 cervical carcinoma patients with mild to moderate depression, high-dose S-ketamine (0.5 mg/kg) significantly reduced pain and depression scores compared to control and other treatment groups at 1 and 3 days post-surgery.

Both low-dose (0.25 mg/kg) and high-dose S-ketamine improved short-term outcomes better than racemic ketamine, with increased serum levels of BDNF and 5-HT, indicating a potential mechanism for its efficacy in managing depression and pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy. Wang, J., Wang, Y., Xu, X., et al.[2021]

In a study of 50 patients undergoing knee surgery, a single intraoperative dose of ketamine significantly reduced postoperative pain and the need for additional pain medication compared to a placebo.

Patients receiving ketamine were able to walk longer on the first postoperative day, indicating improved functional outcomes alongside enhanced pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. Menigaux, C., Guignard, B., Fletcher, D., et al.[2019]

Citations

1. jvascsurg.org jvascsurg.org/article/S0741-5214(24)01989-X/fulltext

Ketamine Reduces Opiate Use and Pain Scores in Patients ... The addition of ketamine to the TAAA SCI protection bundle significantly reduces postoperative opioid use and improves pain scores.

2. withpower.com withpower.com/trial/phase-3-aortic-aneurysm-thoracic-11-2020-1450c

Ketamine for Aortic Aneurysm Pain Management This trial is testing low doses of ketamine to see if it can reduce pain and the need for opioids in patients having a specific type of heart surgery.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470357/

Ketamine - StatPearls - NCBI Bookshelf - NIH A wealth of evidence indicates the value of ketamine in treating severe pain, including conditions such as trauma, fractures, abdominal and ...

4. accjournal.org accjournal.org/journal/view.php?number=1519

The impact of ketamine on outcomes in critically ill patients Our outcomes were mortality, pain, opioid and midazolam requirements, delirium rates, and ICU length of stay. Results: Twelve RCTs involving 805 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0885392401003402

Original article “Burst” Ketamine for Refractory Cancer Pain Analysis of results according to pain mechanisms showed that 15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who appeared to respond, it is ...

6. trialx.com trialx.com/clinical-trials/listings/247114/ketamine-in-patients-undergoing-tevar-procedures-receiving-nci/

Ketamine in Patients Undergoing TEVAR Procedures ... Data indicate that patients receiving NCI experience elevated post-operative pain scores and increased opioid requirements during the 48-hr post ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12055169/

Safety considerations and risk mitigation strategies for ... Focused on ketamine use in anesthesia, pain management, or psychiatric treatment. Addressed safety concerns, adverse effects, or risk mitigation strategies.

8. vascularspecialistonline.com vascularspecialistonline.com/ketamine-reduces-postoperative-opiate-use-and-pain-scores-as-part-of-spinal-cord-protection-protocol-for-taaa-repair/

Ketamine reduces postoperative opiate use and pain ... The estimated six-hour mean pain score for the cohort given ketamine, meanwhile, was 1.9 (95% CI 0.4–3.4) vs. 4.2 (95% CI 2.6–5.8) for those who ...