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NCT Number: NCT04635852

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

"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.

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Key information

Conditions

Cancer Cardiovascular Diseases Dyspnea Dyspnea, Paroxysmal Heart Diseases Heart Failure Neoplasms Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University Hospital Göttingen Center of Palliative Medicine, Göttingen, Hesse, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically or cytologically proven cancer of any entity which is non-curable as judged by the referring physician or investigator
  • To be an inpatient during the study
  • Refractory breathlessness - this study applies only to 'refractory breathlessness ' and is defined: a patient is still breathless although the underlying disease (e.g. lung cancer) or cause of breathlessness (e.g. pleural effusion) is treated optimal as judged by the referring physician or investigator
  • History of recurrent episodic breathlessness - episodic breathlessness is defined as an increase in breathlessness occurring intermittently in patients with or without underlying continuous breathlessness
  • Peak intensity of episodic breathlessness ≥ 3 (NRS, 0-10)
  • Opioid tolerance for at least one day - opioid tolerance is defined: patient who receive per day at least 30mg oral morphine, 15mg oral oxycodone, 4mg oral hydromorphone, 12µg/h transdermal fentanyl or an analgetic equivalent of a different opioid or a different routes of application
  • Life expectancy of at least one month as judged by the referring physician or investigator

Exclusion criteria

  • Uncontrolled breathlessness (i.e. rapidly worsening breathlessness requiring urgent medical or technical intervention)
  • Uncontrolled performance status (i.e. rapid deterioration of performance status)
  • Consideration of any reason by the referring therapeutic team that the patient is not an appropriate participant of a clinical trial
  • Respiratory depression or preconditions with risk of respiratory depression
  • Acute abdomen or ileus or any situation that drug resorption is not possible
  • Renal dysfunction with creatinine clearance (eGFR) calculated as less than 25 ml/minute
  • Medical history of severe hepatic impairment
  • The use of fentanyl transmucosal products for breakthrough cancer pain (BTCP) during the trial
  • The use of a monoamine oxidase inhibitors within the previous 14 days
  • Treatment with any other investigational drugs within the previous 10 days

Treatment and study plan

Fentanyl

Drug

Other names: Fentanyl buccal tablet, Fentanyl citrate

Immediate release morphine

Drug

Other names: Morphine Solution

Primary outcomes

  1. Time to onset of meaningful breathlessness relief

    Time frame: 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 outcomes

  1. Breathlessness intensity

    Time frame: 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)

  2. Numbers of rescue medication doses

    Time frame: 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.

  3. Patient's & investigator's satisfaction

    Time frame: 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).

  4. Preferences of study drugs

    Time frame: through study completion, day 10 (e.g. final visit)

    FBT or IRM or both/none

Other outcomes

  1. Number of (serious) adverse events (AE/SAE; Safety of FBNT/IRM)

    Time frame: through study completion, day 10 (e.g. final visit)

    Counts of adverse events

  2. Severity of AE/SAE (Safety of FBNT/IRM)

    Time frame: through study completion, day 10 (e.g. final visit)

    CTCAE tool v4.03 (National Cancer Institute Common Terminology Criteria)

  3. Oxygen saturation (Safety of FBNT/IRM)

    Time frame: through study completion, day 10 (e.g. final visit)

    finger clip pulse oximetry (Contec Medical Systems Co., China)

  4. Patient's vigilance (Safety of FBNT/IRM)

    Time frame: through study completion, day 10 (e.g. final visit)

    Glasgow Coma Scale (GCS)

  5. Respiratory rate (Safety of FBNT/IRM)

    Time frame: through study completion, day 10 (e.g. final visit)

    breaths per minute

  6. Enrollment rate (Feasibility of study procedures)

    Time frame: day 10 (e.g. final visit)

    Ratio of patients screened to patient with informed consent

  7. Completion rate (Feasibility of study procedure)

    Time frame: day 10 (e.g. final visit)

    Ratio of patients that were randomly assigned to the experimental vs active comparator arm to patients that completed the study

  8. Drop outs (Feasibility of study procedures)

    Time frame: day 10 (e.g. final visit)

    Counts of drop out per visit (TPh+EPh)

  9. Reasons for rejection of study participation of screened patient (Feasibility of study procedures)

    Time frame: day 10 (e.g. final visit)

    List of reasons/ free text responses

  10. Acceptability of study procedures

    Time frame: day 10 (e.g. final visit)

    closed questions: 4-point verbal rating scale between 0=poor/unsatisfied and 4=excellent/very satisfied, and yes/no; reports by patients, investigators and clinical team

  11. Acceptability of measurement tools

    Time frame: day 10 (e.g. final visit)

    closed questions: 4-point verbal rating scale between 0=poor/unsatisfied and 4=excellent/very satisfied, and yes/no; reports by patients, investigators and clinical team

  12. Acceptability of rescue procedures

    Time frame: day 10 (e.g. final visit)

    closed questions: 4-point verbal rating scale between 0=poor/unsatisfied and 4=excellent/very satisfied, and yes/no; reports by patients, investigators and clinical team

Sponsors and collaborators

Lead sponsor

University of Cologne

Other

Collaborators

  • Teva Branded Pharmaceutical Products R&D, Inc.

Registry information

Official study title

Effentora® for Dyspnoea - Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Cancer Patients: A Multicenter, Open Label, Randomized, Morphine-controlled, Crossover, Phase II-TRIAL

Acronym: EFFENDYS

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Nov 19, 2020
Registry last updated
Nov 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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