Propofol vs Sevoflurane for Anesthesia

(ICHOR Trial)

Overseen By Hannah Wiseman

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Matthew Borzage

Must not be taking: QT prolonging drugs

Disqualifiers: MRI-incompatible devices, Preterm infants, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: Approximately 60 minutes

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two anesthesia drugs, propofol and sevoflurane, affect blood flow and oxygen use in the brain during MRI scans. The researchers aim to determine if one drug better maintains healthy brain function under anesthesia. They seek infants up to 1 year old who require anesthesia for an MRI and do not have conditions affecting brain oxygen use or blood flow. Participants will be randomly assigned to receive one of the two drugs during their scan. This research could help doctors make better anesthesia choices for future patients. As a Phase 4 trial, it involves FDA-approved drugs and aims to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking drugs that can prolong the QT interval, you may not be eligible to participate.

What is the safety track record for propofol and sevoflurane?

Research has shown that both propofol and sevoflurane are generally safe. Propofol is often used for anesthesia and sedation. Some studies mention side effects such as an irregular heartbeat and, in rare cases, fever or chills, though these reactions are uncommon.

Sevoflurane, another widely used anesthesia, is also considered safe. Most reported side effects include low blood pressure and breathing problems. With nearly 30 years of use, many of its side effects are well-known.

The FDA has approved both propofol and sevoflurane for clinical use, indicating a well-understood safety profile. While side effects can occur, they are usually manageable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these anesthesia treatments, Propofol and Sevoflurane, because they offer distinct benefits over standard anesthesia options. Propofol is administered as an injectable solution, providing a rapid onset of anesthesia, which is particularly useful for short procedures like MRIs. On the other hand, Sevoflurane is a volatile liquid inhaled as a gas, offering smooth and quick adjustments to anesthesia depth, making it ideal for procedures where flexibility in anesthesia levels is crucial. These unique delivery methods and their ability to provide controlled anesthesia are what make them stand out in the field.

What evidence suggests that this trial's treatments could be effective for anesthesia?

This trial will compare Propofol and Sevoflurane as anesthesia options for MRIs. Research has shown that both treatments are effective. Participants in the Propofol arm will receive this treatment, known for its strong calming effects and reduced confusion upon waking, maintaining high scan quality in 85% of cases. Meanwhile, participants in the Sevoflurane arm will receive this treatment, appreciated for its quick onset and fast recovery, proving effective in 96.6% of patients with minimal impact on heart and lung function. Both treatments offer unique benefits that may better suit different patient needs. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew Borzage, PhD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for patients needing clinical anesthesia for an MRI, including those with conditions affecting brain oxygen or blood flow. It's open to infants up to 1 year old without medical issues that favor one anesthetic over another. Excluded are those with MRI-incompatible devices, certain genetic risks like Long QT Syndrome, and preterm infants under 25 weeks PMA.

Inclusion Criteria

I am a patient under 1 year old.

I have a condition that affects oxygen use or blood flow in my brain.

I need anesthesia for my MRI scans.

Exclusion Criteria

I am at risk for propofol infusion syndrome due to existing health issues.

Patients with an MRI-incompatible device or implant (e.g. pacemakers, stents)

My baby was born before 25 weeks of pregnancy and is still under that age.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive either propofol or sevoflurane anesthesia during their MRI to assess cerebral blood flow and oxygen metabolism

Approximately 60 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

1 visit (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Propofol
• Sevoflurane

Trial Overview The study compares the effects of two anesthetics—Propofol and Sevoflurane—on cerebral blood flow and oxygen metabolism during MRI procedures in a randomized controlled setup where participants are chosen by chance to receive one of the two drugs.

How Is the Trial Designed?

Group I: Sevoflurane Experimental Treatment 1 Intervention

Subject will receive sevoflurane anesthesia during their MRI. Dosage form: volatile liquid for inhalation Dosing: 0-1 month full term neonate (3.3% in oxygen), 1-6 months old (3% in oxygen), 6 months to \<3 years old (2.8% in oxygen), or as per clinical standard of care appropriate for specific subjects. Frequency and duration: continuous infusion while undergoing MRI.

Group II: Propofol Experimental Treatment 1 Intervention

Subject will receive propofol anesthesia during their MRI. Dosage form: injectable solution. Dosage: 100-300 mcg/kg/min, or as per clinical standard of care appropriate for specific subjects. Frequency and duration: continuous infusion while undergoing MRI.

Who Is Running the Clinical Trial?

Matthew Borzage

Lead Sponsor

Trials

1

Recruited

30+

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

Published Research Related to This Trial

Fluorouracil (5-FU) combined with levamisole is the standard treatment for node-positive colon cancer, showing significant benefits in disease-free and overall survival without long-term side effects.

While 5-FU can be enhanced with leucovorin to improve response rates and survival, other combinations like semustine have raised safety concerns, limiting their use despite some initial efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment approaches in colorectal cancer. Grem, JL.[2018]

UFT combined with leucovorin shows equivalent antitumor efficacy to intravenous 5-FU plus leucovorin in treating advanced colorectal cancer, but with reduced toxicity, making it a safer option.

UFT may offer a more convenient treatment method with fewer complications, and it is also being explored for effectiveness in breast cancer treatment, pending FDA approval for its use in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UFT in the treatment of colorectal and breast cancer. Sun, W., Haller, D.[2013]

In a study involving 32 colon cancer patients, administration of Modufolin® resulted in significantly higher levels of the active folate metabolite, methyleneTHF, in both tumor and mucosal tissues compared to Isovorin® (levo-leucovorin).

The increased concentrations of methyleneTHF after Modufolin® administration suggest it may enhance the efficacy of 5-fluorouracil-based chemotherapy, warranting further clinical evaluation as a potential alternative to Isovorin®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacokinetic and pharmacodynamic investigation of Modufolin® compared to Isovorin® after single dose intravenous administration to patients with colon cancer: a randomized study. Wettergren, Y., Taflin, H., Odin, E., et al.[2021]

The combination of Leucovorin (LV) and 5-fluorouracil (5-FU) enhances the effectiveness of 5-FU in treating colorectal cancer, making it a standard therapy worldwide.

In Japan, Levofolinate calcium (I-LV) combined with 5-FU has been clinically proven effective for gastric and colorectal cancer, receiving official approval in 1999.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination of levofolinate calcium and 5-fluorouracil]. Sasaki, T.[2013]

Folfox4 has become the new standard treatment for colorectal cancer, particularly after the Mosaic study, while oral fluoropyrimidines like capecitabine offer effective alternatives to traditional intravenous treatments.

In stage II colon cancer, chemotherapy may not be necessary for low-risk tumors, but high-risk tumors should consider adjuvant treatments like Folfox4 or fluoropyrimidine combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of colorectal cancer]. Segura, C., Afchain, P., de Gramont, A., et al.[2018]

In a study of 194 children undergoing surgery, the combination of propofol and sevoflurane resulted in faster recovery times and more stable vital signs compared to sevoflurane alone, indicating enhanced safety and efficacy in pediatric anesthesia.

The use of both anesthetics significantly reduced the incidence of postoperative agitation, nausea, and vomiting, making it a safer option for children, especially those aged 6 years and younger.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison analysis of safety profiles and identification of risk factors for postoperative adverse reactions: propofol versus sevoflurane in pediatric anesthesia. Xu, X., Liu, H., Yang, J., et al.[2023]

In a study involving 143 adult patients, sevoflurane was found to allow for a quicker recovery from general anesthesia compared to isoflurane, with shorter times for extubation, eye opening, and command response.

Both sevoflurane and isoflurane demonstrated similar safety profiles, as there were no significant differences in renal and hepatic function before and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance and recovery characteristics of sevoflurane anaesthesia in adult patients. A multicenter, randomized comparison with isoflurane. Ranieri, R., Martinelli, G., Pagani, I., et al.[2018]

Desflurane allowed for significantly faster recovery times, specifically in time to eye-opening, compared to sevoflurane and isoflurane, making it a quicker option for ambulatory surgeries.

Isoflurane was found to be the most cost-effective anesthetic agent, with lower overall costs while maintaining comparable safety and recovery profiles to sevoflurane and desflurane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Comparison of Isoflurane versus Sevoflurane and Desflurane for Maintenance of Ambulatory Anesthesia. Kurhekar, P., Vinod, K., Krishna, JSD., et al.[2022]

In a study involving 555 patients undergoing surgery, sevoflurane was found to allow for a faster recovery from anesthesia compared to isoflurane, with patients emerging and responding to commands significantly quicker.

Both sevoflurane and isoflurane had similar safety profiles, but a higher percentage of patients (48%) in the sevoflurane group experienced no adverse effects compared to 39% in the isoflurane group, suggesting sevoflurane may provide a smoother clinical experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients. Campbell, C., Andreen, M., Battito, MF., et al.[2019]

Desflurane anesthesia was associated with a significantly higher rate of respiratory complications (20.0%) compared to sevoflurane (12.8%), indicating that desflurane may pose more risks in terms of airway irritation during ambulatory surgery.

While desflurane allowed for faster eye opening after anesthesia (about 3.32 minutes quicker), there was no significant difference in the time to discharge from the operating room compared to sevoflurane, suggesting that the benefits of quicker recovery may not outweigh the increased respiratory risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse respiratory events with sevoflurane compared with desflurane in ambulatory surgery: A systematic review and meta-analysis. Chen, WS., Chiang, MH., Hung, KC., et al.[2022]

Sevoflurane induction of anesthesia is slower compared to propofol, taking an average of 2.0 minutes versus 0.8 minutes, respectively, indicating that propofol may be more efficient for quick anesthesia onset.

Patients receiving sevoflurane experienced higher rates of nausea and vomiting post-anesthesia compared to those receiving propofol, suggesting that while sevoflurane is effective, it may have a less favorable side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison: the efficacy of sevoflurane-nitrous oxide or propofol-nitrous oxide for the induction and maintenance of general anesthesia. Lien, CA., Hemmings, HC., Belmont, MR., et al.[2019]

In a study of 453 adult surgical inpatients, propofol and sevoflurane did not show significant advantages in recovery rate or quality compared to thiopental and isoflurane during elective surgeries.

While propofol caused more pain on injection, it resulted in less coughing during induction and reduced early postoperative nausea and vomiting, indicating some benefits despite no overall improvement in recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Part I: propofol, thiopental, sevoflurane, and isoflurane-A randomized, controlled trial of effectiveness. Myles, PS., Hunt, JO., Fletcher, H., et al.[2019]

In a study of 60 patients undergoing open cholecystectomy, both sevoflurane and propofol provided similar early recovery profiles, with no significant differences in recovery times for eye opening, following commands, or extubation.

Propofol demonstrated a lower incidence of post-operative nausea and vomiting (PONV) compared to sevoflurane, highlighting its potential advantage due to its intrinsic antiemetic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of recovery profile for propofol and sevoflurane anesthesia in cases of open cholecystectomy. Singh, SK., Kumar, A., Mahajan, R., et al.[2020]

This study will compare the effects of propofol and sevoflurane on the incidence of postoperative delirium in 298 elderly patients undergoing spine surgery, aiming to determine which anesthetic may reduce delirium risk.

The primary outcome is the incidence of delirium within 7 days post-surgery, with secondary outcomes including the timing and duration of delirium, recovery metrics, and other postoperative complications, which could guide better anesthesia choices for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of propofol versus sevoflurane on the incidence of postoperative delirium in elderly patients after spine surgery: study protocol of a randomized controlled trial. Wang, JH., Lv, M., Zhang, HX., et al.[2022]

In a study of 160 patients undergoing elective gastrointestinal surgery, the combination of propofol and sevoflurane for anesthesia maintenance resulted in significantly faster awakening and extubation times compared to sevoflurane alone.

The propofol/sevoflurane regimen also led to a lower incidence of serious coughing and agitation during recovery, enhancing patient comfort without compromising other recovery metrics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sevoflurane/propofol coadministration provides better recovery than sevoflurane in combined general/epidural anesthesia: a randomized clinical trial. Liang, C., Ding, M., Du, F., et al.[2021]

Citations

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A randomized trial evaluating low doses of propofol ... The use of low doses of propofol infusion did not adversely affect the overall scan quality in our study, which was excellent in 85%, good in 13% and poor in ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825749

Pulmonary Atelectasis After Sedation With Propofol vs ... We expected the incidence of atelectasis in the propofol-ketamine group to decrease by 35% compared with the propofol group.

4. sciencedirect.com sciencedirect.com/science/article/pii/S000709121734240X

Propofol-based sedation regimen for infants and children ... Sedation failure rates up to 20% and inadequate sedation up to 22.5% are reported depending on the sedation regimen used. This is in contrast to our results, ...

5. oncotarget.com oncotarget.com/article/22271/text/

Dexmedetomidine versus propofol on the sedation of ... Propofol should be encouraged in pediatric patients undergoing MRI for its better sedative effects and a low incidence of emergence delirium.

6. piramalcriticalcare.us piramalcriticalcare.us/wp-content/uploads/2021/12/MSDS_Propofol_Injectable_Emulsion_060214.pdf

1 SAFETY DATA SHEET Product Name: Propofol Injectable ... Reproductive Effects: continued However, propofol has been shown to cause maternal deaths in rats and rabbits and decreased pup survival during the lactating ...

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Propofol Injectable Emulsion 1. CHEMICAL PRODUCT ... Reproduction studies performed in rats and rabbits at intravenous dosages of 15 mg/kg/day have revealed no evidence of harm to the fetus due to ...

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Propofol (marketed as Diprivan and as generic products) ... FDA has tested multiple units of propofol vials and lots used in patients who have experienced these symptoms and to date, these tests have not ...

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(67) Propofol Sedation Safety Data | Pediatrics Propofol was discontinued secondary to possible adverse effects in two patients. One developed an arrhythmia. The other was uremic with concern ...

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The Propofol Safety Review The FDA released a safety alert concerning reports over the past few months of cases of fever, chills, and body aches in several clusters of patients shortly ...