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Effect of Sublingual Fentanyl on Breathlessness in COPD

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ClinicalTrials.gov Identifier: NCT04004117
Recruitment Status : Not yet recruiting
First Posted : July 1, 2019
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
Jean Bourbeau, MD, McGill University

Brief Summary:
There is actually no physiologic or clinical data in the literature to clearly define the potential benefits and side effects of sublingual fentanyl in patients with COPD. Therefore, the purpose of this study is to test the hypothesis that sublingual fentanyl will improve exercise capacity and dyspnea control in severe COPD patients experiencing persistent breathlessness despite optimal management.

Condition or disease Intervention/treatment Phase
Copd Drug: Fentanyl citrate solution sublingual Drug: Placebo oral liquid Phase 2 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Single centre randomized clinical trial, double-blinded, cross-over design, comparing fentanyl sublingual at a dose 12,5 mcg to placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

All research staff, treating clinicians, analysts and patients will remain blinded to the treatment allocation.

Unbinding will only occur in emergency situations following consultation with the principal investigator and at the conclusion of collecting the last data point for the last participant in the entire study.

Primary Purpose: Treatment
Official Title: Effect of Sublingual Fentanyl on Breathlessness in COPD : A Randomized Cross-over Trial
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fentanyl s/l
Sublingual fentanyl will consist in liquid fentanyl at a concentration of 25 mcg/mL, with preparation by the pharmacist of pre-dosed syringes of 12,5 mcg (0,5 mL).
Drug: Fentanyl citrate solution sublingual
Solution of fentanyl citrate (DIN : 02384124 / 02240434 / 02385406) will be administered sublingually by syringe. The dose is 12,5 mcg.

Drug: Placebo oral liquid
Placebo will consist in simple syrup (simple syrup B.P. - NPN: 00050121) administered sublingually with syringe.

Placebo Comparator: Placebo
Placebo will consist in simple syrup (simple syrup B.P. - NPN: 00050121) administered sublingually with syringe.
Drug: Fentanyl citrate solution sublingual
Solution of fentanyl citrate (DIN : 02384124 / 02240434 / 02385406) will be administered sublingually by syringe. The dose is 12,5 mcg.

Drug: Placebo oral liquid
Placebo will consist in simple syrup (simple syrup B.P. - NPN: 00050121) administered sublingually with syringe.




Primary Outcome Measures :
  1. Breathlessness [ Time Frame: Up to 10 days after visit 1 ]
    Post-dose difference in exertional breathlessness at isotime (isotime definition : highest equivalent 2 min interval of exercise completed by a given participant).

  2. Exercise capacity [ Time Frame: Up to 10 days after visit 1 ]
    Post-dose difference in exercise endurance time (EET)


Secondary Outcome Measures :
  1. Number and description of adverse effects [ Time Frame: Up to 48 hours after treatment administration ]
    Number and description of adverse effects

  2. Locus of Symptoms [ Time Frame: Up to 10 days after visit 1 ]
    Percentage contribution of breathlessness and leg discomfort to exercise cessation

  3. Qualitative descriptors of breathlessness at end exercise [ Time Frame: Up to 10 days after visit 1 ]
    Description by patients of the characteristics of breathlessness at the end of exercise

  4. Change in multidimensional evaluation of dyspnea [ Time Frame: Up to 10 days after visit 1 ]
    Evaluation of the multidimensional components of dyspnea following each intervention and using the Multidimensional Dyspnea Profile (MDP) questionnaire. The questionnaire contains a total of 11 questions to characterize dyspnea. Each questions is a symptom or a sensation that need to be rated on scale from 0 to 10 depending on the intensity of the symptom/sensation, with 0 representing the absence of symptom and 10 representing the higher perception of symptom. There is no combination to form a total score.

  5. Participant blinded preference [ Time Frame: Up to 10 days after visit 1 ]
    At the last visit, the investigators will ask to patients which intervention they preferred regarding relief of breathlessness and comfort during exercise

  6. Difference in the locus of symptoms limiting exercise during a cardio-pulmonary exercise test response when comparing responders to non-responders. [ Time Frame: Up to 10 days after visit 1 ]
    Responders will be define as participant with ≥ 1-point improvement in Borg dyspnea. The locus of symptom is the symptom that limit the exercise test (breathlessness, leg fatigue or both).



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged > 40 years
  • Cigarette smoking history ≥10 pack years
  • Clinical diagnosis of severe to very severe COPD, i.e. post-β2-agonist FEV1 <50% and FEV1/FVC <0.70
  • Chronic activity-related dyspnea, define as any one or combination of a modified MRC of 3-4 or a BDI focal score ≤ 8
  • Uncontrolled daily activity-related dyspnea despite optimal medical treatment, including oral morphine treatment at a dose of a least 4 mg per day
  • No change in medication dosage or frequency of administration in the previous 2 weeks
  • No exacerbations or hospitalizations in the preceding 4 weeks

Exclusion Criteria:

  • CO2 retention, defined as a resting arterialized capillary (earlobe) PCO2 of >50 mmHg
  • Self-reported history of addiction/substance abuse
  • Acute alcoholism
  • Presence of important contraindications to cardiopulmonary exercise testing (CPET)
  • History of hypersensitivity to fentanyl or any component of the formulation
  • Actual use of methadone
  • Concurrent use or use within 14 days of a monoamine oxidase (MAO) inhibitor
  • Severe CNS depression
  • Convulsive disorders
  • Known or suspected mechanical GI obstruction (e.g., bowel obstruction or strictures) or any diseases/conditions that affect bowel transit (e.g., ileus of any type)
  • Increased cerebrospinal or intracranial pressure and head injury
  • Active mouth mucositis
  • Dementia diagnosis or significant neurocognitive problems
  • History of severe chronic kidney disease (stage 4-5)
  • Women of child bearing potential (defined as not having gone at least 12 months without a menstrual period) will be required to take a routine (urine) pregnancy test to rule out the possibility of pregnancy
  • Breast-Feeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04004117


Contacts
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Contact: Jean Bourbeau, MD 5149440126 jean.bourbeau@mcgill.ca
Contact: Sebastien Gagnon, MD 18195712730 sebastien.gagnon3@mail.mcgill.ca

Sponsors and Collaborators
McGill University
Investigators
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Principal Investigator: Jean Bourbeau, MD Reseach Institute MUHC

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Responsible Party: Jean Bourbeau, MD, Professor, McGill University
ClinicalTrials.gov Identifier: NCT04004117     History of Changes
Other Study ID Numbers: RIMUHCCOPDJB
First Posted: July 1, 2019    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to have the data share by other researcher. All data will be denominalized in order to respect privacy. Data will be collected in an anonymous data sheet, protected by a password. Only investigators and statistician will have access to this data sheet.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Dyspnea
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Fentanyl
Citric Acid
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action