Intranasal Fentanyl for Procedural Pain

(INFENT PICC Trial)

Overseen By Najla Tabbara, PharmD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Mount Sinai Hospital, Canada

Must not be taking: Opioids, Sedatives, CYP3A4 inhibitors

Disqualifiers: Choanal atresia, Facial anomalies, Genetic conditions, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

8 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this feasibility clinical trial is to explore the role of intranasal fentanyl for pain associated with PICC placement in preterm infants. The primary goals are identifying whether enough infants join the study and complete the study procedures.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you are receiving continuous intravenous infusions or scheduled enteral doses of opioids or sedatives within 12 hours of PICC placement, or if you are prescribed strong CYP3A4 inhibitors, you cannot participate in the trial.

What data supports the idea that Intranasal Fentanyl for Procedural Pain is an effective drug?

The available research shows that intranasal fentanyl is effective for managing pain. It has a fast onset of action, starting to work in about 7 minutes, and lasts for about an hour. It is especially useful for breakthrough pain in cancer patients, where it has been shown to be superior to oral fentanyl. Intranasal fentanyl is also effective for acute pain in both children and adults in hospital settings, offering similar pain relief to intravenous and oral fentanyl or morphine. Additionally, it is easier to administer and works faster than some other forms, like oral transmucosal fentanyl, making it a good option for patients with oral issues due to cancer treatment. ^{1 2 3 4 5}

What safety data exists for intranasal fentanyl?

Intranasal fentanyl has been shown to be rapidly and efficiently absorbed, with products like PecFent/Lazanda and Instanyl developed to treat breakthrough pain in cancer patients. These products offer advantages such as faster onset and easier administration compared to oral transmucosal products. Safety features are expected in packaging, and risk management protocols may be required due to fentanyl's nature. Intranasal fentanyl has demonstrated safety and efficacy for acute pain management in emergency settings, and its use is promising for additional indications and pediatric use. ^{3 4 6 7 8}

Is the drug Fentanyl, used in the trial 'Intranasal Fentanyl for Procedural Pain', a promising treatment?

Yes, intranasal fentanyl is a promising treatment. It is quickly absorbed through the nose, providing fast pain relief, which is especially useful for managing sudden pain in cancer patients and in emergency situations. It is easy to administer, even in challenging environments, and has been shown to be effective for both adults and children. ^{1 3 4 9 10}

Research Team

Vibhuti Shah, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

This trial is for preterm infants who need a PICC (a type of long-term IV) placed. The study aims to see if enough babies can join and finish the study procedures.

Inclusion Criteria

Infants considered medically appropriate for the study by the most responsible physician

My baby was born before 32 weeks or weighed less than 1.5 kg.

Exclusion Criteria

My infant is on continuous IV or regular oral doses of pain or sedative meds.

My infant has a blocked nasal passage or nosebleeds.

Infants with facial anomalies

Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 months

Treatment

Participants receive either intranasal fentanyl or normal saline 10 minutes before PICC placement

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse events and pain score assessment

Up to 6 hours

1 visit (in-person)

Treatment Details

Interventions

• Fentanyl

Trial Overview The trial is testing intranasal fentanyl, a pain medication, against normal saline (saltwater solution). It's to see if fentanyl can help manage pain during PICC placement in these infants.

Participant Groups

Group I: Intranasal fentanyl plus standard of care Experimental Treatment 1 Intervention

One dose of fentanyl 1.5 µg/kg via a mucosal atomization device 10 minutes before the PICC placement. Standard of care includes sucrose 24% oral solution with or without non-nutritive sucking.

Group II: Intranasal normal saline plus standard of care Placebo Group 1 Intervention

One dose of normal saline (volume equivalent to fentanyl 1.5 µg/kg) via a mucosal atomization device 10 minutes before the PICC placement. Standard of care includes sucrose 24% oral solution with or without non-nutritive sucking.

Fentanyl is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fentanyl for:

• Pain management
• Anesthesia

Approved in European Union as Fentanyl for:

• Severe pain
• Breakthrough pain in cancer patients

Approved in Canada as Fentanyl for:

• Pain relief
• Neuropathic pain

Approved in Japan as Fentanyl for:

• Cancer pain
• Postoperative pain

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Recruited

70,700+

Findings from Research

Intranasal fentanyl is a highly effective option for managing cancer and chronic pain, with a bioavailability of 89% and a rapid onset of action (approximately 7 minutes).

It has been shown to provide superior relief for cancer breakthrough pain compared to oral transmucosal fentanyl, while maintaining a similar safety profile to intravenous and oral fentanyl or morphine in both children and adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal fentanyl: from pharmacokinetics and bioavailability to current treatment applications. Panagiotou, I., Mystakidou, K.[2013]

Fentanyl sublingual tablets provide rapid pain relief for opioid-tolerant cancer patients, significantly reducing pain intensity compared to placebo within 15 minutes after administration, as shown in two randomized clinical trials.

The treatment was well tolerated, with most side effects being mild to moderate, and nearly half of the patients reported being satisfied or very satisfied with their pain management using fentanyl sublingual.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fentanyl sublingual: in breakthrough pain in opioid-tolerant adults with cancer. Chwieduk, CM., McKeage, K.[2021]

Intranasal fentanyl is rapidly absorbed and offers a promising method for pain management, particularly for breakthrough pain in cancer patients, with advantages over oral forms such as faster onset and easier administration.

New formulations of fentanyl nasal sprays, like PecFent and Instanyl, are designed to minimize runoff and improve absorption, making them more effective while also requiring lower volumes for effective dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal delivery of fentanyl. Watts, P., Smith, A., Perelman, M.[2018]

The intranasal route for medication delivery is gaining popularity in emergency settings due to its speed and ease of use, especially for patients who cannot receive intravenous access.

Midazolam and fentanyl administered intranasally have shown effectiveness and safety for sedation and pain management, while the use of intranasal naloxone for opioid overdose is also supported, although the roles of ketamine and dexmedetomidine remain less clear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When to Pick the Nose: Out-of-Hospital and Emergency Department Intranasal Administration of Medications. Rech, MA., Barbas, B., Chaney, W., et al.[2017]

The new Cygnus transdermal fentanyl device demonstrated significant variability in fentanyl absorption rates, with some patients experiencing rapid absorption that led to clinically significant fentanyl toxicity, necessitating early removal of the device.

The bioavailability of the transdermal fentanyl was found to be 63% with a wide range of plasma concentrations, indicating that while it may offer a noninvasive delivery method, its safety for postoperative use is questionable due to the risk of overdose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biopharmaceutics of a new transdermal fentanyl device. Fiset, P., Cohane, C., Browne, S., et al.[2019]

The 12 microg/h fentanyl transdermal patch was effective in treating moderate to severe pain over a 28-day trial with 227 patients, showing significant improvement in pain levels and overall therapy assessments.

The safety profile of the lower dose patch was comparable to higher doses, with no unexpected adverse events and a lower drop-out rate, making it particularly suitable for elderly or opioid-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study to assess the clinical utility of low-dose fentanyl transdermal system in patients with chronic nonmalignant pain. Otis, J., Rothman, M.[2013]

The study demonstrated that the single-dose delivery system (SDS) of intranasal fentanyl spray (INFS) is pharmacokinetically bioequivalent to the multi-dose delivery system (MDS), with similar peak plasma concentrations and overall drug exposure in 48 healthy subjects.

Both delivery systems showed consistent safety profiles, with no safety concerns identified when INFS was administered alongside oral naltrexone to prevent adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose and multi-dose delivery systems for intranasal fentanyl spray are bioequivalent as demonstrated in a replicate pharmacokinetic study. Nave, R., Connolly, SM., Popper, L., et al.[2013]

The FDA has approved a new nasal spray formulation of fentanyl, called Lazanda-Archimedes, specifically for managing breakthrough pain in adult cancer patients who are already tolerant to opioid therapy.

This approval adds to the existing forms of fentanyl available in the US, which include intravenous, intrathecal, epidural, transdermal, and oral transmucosal options, providing more flexibility in pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fentanyl nasal spray (Lazanda) for pain. [2013]

Intranasal (IN) fentanyl was found to effectively reduce procedural pain in preterm infants, as indicated by a significant decrease in pain scores after administration, with a mean difference of 1.3 points on the Premature Infant Pain Profile.

The study, involving 13 infants and 22 procedures, reported no significant changes in physiological parameters after IN fentanyl administration, suggesting it is a safe alternative for pain management, although two adverse events (one apnea and one desaturation) were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Fentanyl for Procedural Analgesia in Preterm Infants. Cheng, C., Tabbara, N., Cheng, C., et al.[2022]

A study involving 247 patients showed that intranasal fentanyl significantly reduced pain scores from an initial average of 8.6 to lower levels at 5, 10, and 15 minutes, indicating its efficacy in pain management (P<0.0001).

No adverse events, such as respiratory depression or the need for naloxone, were reported, highlighting the safety of using intranasal fentanyl for pain relief in challenging environments like ski resorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol. Lynch, TV., Callas, PW., Peterson, TD., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Intranasal fentanyl: from pharmacokinetics and bioavailability to current treatment applications. [2013]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Fentanyl sublingual: in breakthrough pain in opioid-tolerant adults with cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Nasal delivery of fentanyl. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

When to Pick the Nose: Out-of-Hospital and Emergency Department Intranasal Administration of Medications. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Biopharmaceutics of a new transdermal fentanyl device. [2019]

6. England pubmed.ncbi.nlm.nih.gov

A Phase III study to assess the clinical utility of low-dose fentanyl transdermal system in patients with chronic nonmalignant pain. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Single-dose and multi-dose delivery systems for intranasal fentanyl spray are bioequivalent as demonstrated in a replicate pharmacokinetic study. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Fentanyl nasal spray (Lazanda) for pain. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Intranasal Fentanyl for Procedural Analgesia in Preterm Infants. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol. [2022]