Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Cancer Patients

Phase 2

Completed

• Conditions: Cancer; Dyspnea, Paroxysmal
• Interventions: Drug: Immediate release morphine; Drug: Fentanyl

• Registration Number: NCT04635852
• Lead Sponsor: University of Cologne

Brief Summary

"Episodic breathlessness (or dyspnea) is one form of chronic refractory breathlessness characterized by a severe worsening of breathlessness intensity or unpleasantness beyond usual fluctuations in the patient's perception. Episodes are time-limited (seconds to hours) and occur intermittently, with or without underlying continuous breathlessness. Episodes may be predictable or unpredictable, depending on whether any trigger(s) can be identified. There is a range of known triggers which can interact (e.g. exertion, emotions, comorbidities or external environment). One episode can be caused by one or more triggers." ( definition by an international expert consensus \[Simon et al. 2013\]). Approximately half of patients with cancer complain about breathlessness with the highest prevalence in pulmonary malignancies. Episodic breathlessness is reported by 81% of breathless cancer patients with significant impairment on quality of life and limitations on activity. Although episodic breathlessness show some similar characteristics like episodes of pain (breakthrough cancer pain, BTCP; median duration 30minutes), they are often shorter: 91% last less than 20minutes (min). Other evidence supports these findings with duration between 2-15minutes which is a real challenge for the treatment of episodic breathlessness. In the majority of cases, episodic breathlessness occur 1-4 times per day and peak intensity is rated moderate or severe.

There is evidence for the effectiveness of opioids for the relief of chronic refractory breathlessness. There is no evaluated and proven standard treatment for the relief of episodic breathlessness at the moment but immediate-release morphine (IRM) as solution or tablet is most frequently used in clinical practice to treat episodic breathlessness. Time to onset of action of IRM is about 20-30min for pain. Fentanyl is a potent opioid and shows good evidence for the treatment of BTCP through its quick onset of action (5-15min) and short duration of action (50-60min). Because of its pharmacodynamic properties fentanyl might be appropriate and effective for the relief of episodic breathlessness. However, the efficacy of fentanyl for the relief of breathlessness and time to onset is unknown.

This pilot study aims to evaluate relative efficacy, feasibility and time to onset of two different opioids (fentanyl and morphine) in order to improve the management of episodic breathlessness.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2014-01-10
• Primary Completion: 2014-11
• Study Completion: 2014-12
• Status Verified: 2020-11
• Study First Submitted QC: 2020-11-13
• Last Update Submitted: 2020-11-13
• Study First Posted: 2020-11-19
• Last Update Posted: 2020-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Immediate release morphine	Immediate release morphine	Immediate release morphine, solution Dosage: Start with a minimum of 5mg (to be determined by titration)
Fentanyl	Fentanyl	Fentanyl buccal tablet Dosage: 100µg - 600 µg Fentanyl (to be determined by titration) Administration: buccal administration (tablet)

Primary Outcome Measures

Name	Time	Method
Time to onset of meaningful breathlessness relief	minutes (by stop watch) from drug application of FBT/IRM up to breathlessness relief	To determine the time to onset of meaningful breathlessness relief of fentanyl buccal tablet (FBT) in comparison to immediate-release morphine (IRM)

Secondary Outcome Measures

Name	Time	Method
Breathlessness intensity	at 0, 3, 5, 10, 15, 20, 30, 45 and 60 minutes after application of FBT/IRM	Breathlessness intensity measured by NRS (range 0-10)
Numbers of rescue medication doses	Numbers of rescue medication doses through study completion, assessed at day 10 (final visit)	If adequate breathlessness relief was not reached after 30 min, the patient could use his standard rescue medication.
Patient's & investigator's satisfaction	through study completion, day 10 (e.g. final visit)	Patient's and investigator's satisfaction of breathlessness relief and route of application regarding ease of administration (4-point verbal rating scale: 0 = poor/unsatisfied and 4 = excellent/very satisfied).
Preferences of study drugs	through study completion, day 10 (e.g. final visit)	FBT or IRM or both/none

Trial Locations

Locations (3)

Study Center Palliative Medicine; 🇩🇪 Cologne, NRW, Germany

University Hospital Göttingen Center of Palliative Medicine; 🇩🇪 Göttingen, Hessen, Germany

Hospital Essen- Mitte, Departement of Palliative Medicine; 🇩🇪 Essen, NRW, Germany