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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether intranasal fentanyl can reduce pain during PICC (a type of catheter) placement in preterm infants. The trial compares fentanyl with a placebo (a harmless substance with no treatment effect) to determine which better manages pain. Infants born before 32 weeks or weighing less than 1.5 kg may qualify if their doctor agrees. The goal is to enroll and retain enough infants to ensure meaningful results. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking pain management for infants.

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.

Is there any evidence suggesting that intranasal fentanyl is likely to be safe for preterm infants?

Research has shown that intranasal fentanyl is generally safe for treating sudden pain in people of all ages, including children. It offers an effective and non-invasive option for pain relief. Studies have found that, when used correctly, it is well-tolerated. Possible side effects include mild sleepiness or nausea, common with many pain medications. However, these effects are usually manageable and not severe. This treatment is already used in medical practice, indicating its safety when administered properly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pain?

Researchers are excited about using intranasal fentanyl for procedural pain because it offers a fast-acting and non-invasive alternative to current pain management options, which often involve oral medications or intravenous delivery. This approach uses a mucosal atomization device to deliver fentanyl directly through the nose, providing rapid pain relief without the need for needles. Additionally, this method can be particularly beneficial for patients who may have difficulty swallowing or for whom IV access is challenging, improving the overall patient experience during procedures like PICC placements.

What evidence suggests that intranasal fentanyl might be an effective treatment for procedural pain in preterm infants?

This trial will compare intranasal fentanyl with a placebo for managing procedural pain. Research has shown that intranasal fentanyl effectively manages pain in children and premature babies. Studies have found that it significantly reduces pain during procedures, as measured by a special pain assessment tool for premature infants. In one small study, intranasal fentanyl relieved pain quickly, starting within 5 minutes and lasting for over 30 minutes. Clinical guidelines recommend it as a safe and easy option for moderate to severe pain relief. Overall, current evidence supports intranasal fentanyl as a promising treatment for pain during procedures in premature infants. ^{1 2 4 6 7}

Who Is on the Research Team?

Vibhuti Shah, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10095441/

Intranasal Fentanyl for Acute Pain Management in Children ... They concluded that INF was effective in relieving pain, with no differences from comparator drugs; only one RCT showed its superiority over IM ...

2. rch.org.au rch.org.au/clinicalguide/guideline_index/intranasal_fentanyl/

Clinical Practice Guidelines : Intranasal fentanyl Intranasal (IN) fentanyl is a safe, non-invasive and effective analgesic for children with moderate to severe pain · Fentanyl should be used in combination with ...

3. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2021.815014/full

Intranasal Fentanyl for Procedural Analgesia in Preterm ... In this small study of preterm infants, we were able to demonstrate the effectiveness of IN fentanyl in reducing procedural pain as assessed by PIPP scores. Our ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735675715007421

Time to opioid administration after implementation of an ... In previous studies, IV fentanyl administered intranasally (1.5 μg/kg) reduced pain within 5 minutes and lasted in excess of 30 minutes [10], [11], [12], [13].

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07112430

Fentanyl Intranasal for Retinopathy of Prematurity ... This double-blinded, randomized controlled trial will evaluate the effectiveness and safety of intranasal fentanyl (INF) in reducing procedural ...

6. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1070685/full

Safety of nurse-directed triage intranasal fentanyl protocol ... Our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management.

7. sciencedirect.com sciencedirect.com/science/article/pii/S240584402310291X

Clinical and pharmacokinetics overview of intranasal ... Intranasal Fentanyl (INF) at a 50 μg/ml concentration decreased renal colic pain to the lowest level in 30 min. Possible adverse effects specific to INF are ...