Pulmonary Arterial HypertensionPhase 2NCT03401476
Effect of Morphine on Dyspnea and 6-Minute Walk Distance in Pulmonary Arterial Hypertension
A Phase 2 study testing Morphine Sulfate in people with Pulmonary Arterial Hypertension, run by John Granton at 1 site in Canada.
Trial summary
Despite advances in treatment and corresponding improvements in survival, patients with pulmonary arterial hypertension (PAH) remain highly symptomatic. In one survey of 315 patients with PAH, sixty-eight percent had moderate or severe dyspnea on exertion and 40% had a profound and clinically significant deficit in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Morphine Sulfate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 8 May 2017to 31 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 or older
- Diagnosis of Group 1 pulmonary hypertension including idiopathic PAH, heritable PAH, and PAH that is drug- or toxin-induced, associated with connective tissue disease, human immunodeficiency virus (HIV) infection, congenital heart disease, or schistosomiasis23
- PAH confirmed by means of a right heart catheterization demonstrating:24
- Mean pulmonary arterial pressure of ≥ 25 mmHg
- Pulmonary capillary wedge pressure ≤ 15 mmHg
- Pulmonary vascular resistance of ≥ 3 Wood units
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- World Health Organization (WHO) Functional Class III or ambulatory Class IV
- Six-minute walk test performed within the past 6 months demonstrating a distance of at least 50 metres.
- Unchanged PAH medication regimen for 30 days prior to enrolment. Therapy may include endothelin-receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, or oral or parenteral prostacyclin analogues. Diuretic doses may change.
Who cannot join
- Group 1 pulmonary hypertension due to portal hypertension
- Group 1 pulmonary hypertension due to pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis
- Groups 2, 3, 4, or 5 pulmonary hypertension
- Severe renal impairment (estimated glomerular filtration rate < 30 mL/minute/1.73m2 measured within 6 months)
- Severe hepatic impairment (INR > 2.0 in absence of vitamin K antagonist therapy, serum bilirubin > 50mmol/L, cirrhosis on imaging or liver biopsy, prior hepatic encephalopathy, or Model for End-Stage Liver Disease (MELD) score > 19, measured within 6 months, as required based on clinical suspicion)
- Women who are pregnant or breastfeeding (beta-human chorionic gonadotropin (hCG) to confirm non-pregnant status in all females below age 50)
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- Hypersensitivity to opioid analgesic, concomitant use with Monoamine Oxidase (MAO) inhibitor or within 14 days of such treatment, concomitant use with barbiturates. Concomitant use with benzodiazepines and/or antipsychotics is permissible provided doses are stable over preceding 1 month.
- Daily use of an opioid-containing medication
- Unstable condition that is a contraindication to opioid use: Central Nervous System (CNS) depression, acute respiratory disease or impairment (acute hypoxia or hypercapnia), acute asthma or Chronic Obstructive Pulmonary Disease (COPD) exacerbation, untreated symptomatic obstructive sleep apnea, unstable cardiac arrhythmias, suspected hypovolemia, recent seizures (within 1 month), active drug abuse, abdominal disease and/or recent GI surgery (within 1 month), active gallbladder disease/biliary colic, untreated depression/suicidality, recent head injury (within 1 month), pre-existing intracranial lesion or increased intracranial pressure, untreated urinary tract obstruction, untreated hypothyroidism, hypopituitarism or Addison's disease.
- Hypotension (resting systolic blood pressure less than or equal to 80mmHg)
- Active or unstable coronary artery disease
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network, Toronto General Hospital
Toronto, Ontario, M5G 2N2
About this study
Despite advances in treatment and corresponding improvements in survival, patients with pulmonary arterial hypertension (PAH) remain highly symptomatic. In one survey of 315 patients with PAH, sixty-eight percent had moderate or severe dyspnea on exertion and 40% had a profound and clinically significant deficit in quality of life. Palliative care is being increasingly investigated in life-limiting cardiovascular diseases to alleviate symptoms. In PAH, its implementation is frequently delayed until end-of-life. Opioids are a common palliative care intervention, however the efficacy and safety of opioids for symptom relief in PAH has not been evaluated.
Read the detailed description
There is biologic plausibility for opioids in the treatment of dyspnea in PAH. Opioids have widespread effects including venodilation, vasodilation, reducing sympathetic outflow, blunting hypercapnic and hypoxic ventilatory responses, and altering the central perception of dyspnea. Although the origins of dyspnea in PAH are incompletely understood and multifactorial, right ventricular dysfunction reduces exercise capacity and likely also plays a role in the development of dyspnea. Mechanoreceptors situated in the right atrium and right ventricle sense elevated pressures and via sympathetic afferents may lead to an augmentation of ventilatory response and hence dyspnea. Morphine may specifically antagonize this feedback loop by causing venodilation and blunting sympathetics. Morphine also reduces central chemosensitivity and perceptions of dyspnea. Therefore, the drug may antagonize both peripheral and central drivers of dyspnea in PAH.
Investigators will conduct a single-center feasibility study of morphine for treatment of dyspnea and exercise intolerance in PAH. Participants will complete two 6-minute walk tests (6MWT) within one week. Participants will be randomly assigned to receive morphine prior to either the first or second 6MWT. Symptoms and 6-minute walk distance (6MWD) will be compared between the two tests.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Morphine Sulfate
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Morphine SulfateDrug
Also called Statex
Morphine Sulfate Tablets
| Study group | Role | What they receive |
|---|---|---|
| Morphine sulfate - Visit 1 | Active comparator | Patients who are randomized to this group will be administered a fixed 5mg dose of oral morphine sulfate prior to performing their 6MWT at Visit 1. Receives: Drug: Morphine Sulfate |
| Morphine sulfate - Visit 2 | Active comparator | Patients who are randomized to this group will be administered a fixed 5mg dose of oral morphine sulfate prior to performing their 6MWT at Visit 2. Receives: Drug: Morphine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Borg Dyspnea Score
Change in peak Borg dyspnea score (morphine versus control)
Measured: The Peak Borg Dyspnea Score will be determined over 6 minutes of observation during the conduct of each 6-minute walk test. The 6-minute walk tests and assessments of the peak Borg Dyspnea Score will be recorded within 1 and 7 days of each other.
Secondary outcomes (1)
Change in 6-Minute Walk Distance
Change in six-minute walk distance (morphine versus control)
Measured: The distance travelled during each 6 minute walk will be determined at completion of the 6-minute walk test. The distance travelled during the 6-minute walk test will be recorded within 1 and 7 days of each other.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start8 May 2017
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- John Granton
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John Granton, University Health Network, Toronto
- Investigators
- John Granton, MD, FRCPC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401476
- Sponsor's protocol ID
- MorPHine
- Status last verified
- Jan 2018
- First submitted
- 30 Apr 2017
- Last updated
- 18 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Morphine on Dyspnea and 6-Minute Walk Distance in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT03401476
- Acronym / sponsor ID
- MorPHine
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- John GrantonUniversity, hospital or other
- Study start
- 8 May 2017 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite advances in treatment and corresponding improvements in survival, patients with pulmonary arterial hypertension (PAH) remain highly symptomatic. In one survey of 315 patients with PAH, sixty-eight percent had moderate or severe dyspnea on exertion and 40% had a profound and clinically significant deficit in quality of life. Palliative care is being increasingly investigated in life-limiting cardiovascular diseases to alleviate symptoms. In PAH, its implementation is frequently delayed until end-of-life. Opioids are a common palliative care intervention, however the efficacy and safety of opioids for symptom relief in PAH has not been evaluated.
Detailed description
There is biologic plausibility for opioids in the treatment of dyspnea in PAH. Opioids have widespread effects including venodilation, vasodilation, reducing sympathetic outflow, blunting hypercapnic and hypoxic ventilatory responses, and altering the central perception of dyspnea. Although the origins of dyspnea in PAH are incompletely understood and multifactorial, right ventricular dysfunction reduces exercise capacity and likely also plays a role in the development of dyspnea. Mechanoreceptors situated in the right atrium and right ventricle sense elevated pressures and via sympathetic afferents may lead to an augmentation of ventilatory response and hence dyspnea. Morphine may specifically antagonize this feedback loop by causing venodilation and blunting sympathetics. Morphine also reduces central chemosensitivity and perceptions of dyspnea. Therefore, the drug may antagonize both peripheral and central drivers of dyspnea in PAH.
Investigators will conduct a single-center feasibility study of morphine for treatment of dyspnea and exercise intolerance in PAH. Participants will complete two 6-minute walk tests (6MWT) within one week. Participants will be randomly assigned to receive morphine prior to either the first or second 6MWT. Symptoms and 6-minute walk distance (6MWD) will be compared between the two tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine sulfate - Visit 1 | Active comparator | Drug: Morphine SulfatePatients who are randomized to this group will be administered a fixed 5mg dose of oral morphine sulfate prior to performing their 6MWT at Visit 1. |
| Morphine sulfate - Visit 2 | Active comparator | Drug: Morphine SulfatePatients who are randomized to this group will be administered a fixed 5mg dose of oral morphine sulfate prior to performing their 6MWT at Visit 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 18 or older
- Diagnosis of Group 1 pulmonary hypertension including idiopathic PAH, heritable PAH, and PAH that is drug- or toxin-induced, associated with connective tissue disease, human immunodeficiency virus (HIV) infection, congenital heart disease, or schistosomiasis23
- PAH confirmed by means of a right heart catheterization demonstrating:24
- World Health Organization (WHO) Functional Class III or ambulatory Class IV
- Six-minute walk test performed within the past 6 months demonstrating a distance of at least 50 metres.
Key exclusion criteria (11 listed)
- Group 1 pulmonary hypertension due to portal hypertension
- Group 1 pulmonary hypertension due to pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis
- Groups 2, 3, 4, or 5 pulmonary hypertension
- Severe renal impairment (estimated glomerular filtration rate < 30 mL/minute/1.73m2 measured within 6 months)
- Severe hepatic impairment (INR > 2.0 in absence of vitamin K antagonist therapy, serum bilirubin > 50mmol/L, cirrhosis on imaging or liver biopsy, prior hepatic encephalopathy, or Model for End-Stage Liver Disease (MELD) score > 19, measured within 6 months, as required based on clinical suspicion)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Morphine SulfateAlso: StatexMorphine Sulfate Tablets | Drug | Morphine sulfate - Visit 1, Morphine sulfate - Visit 2 |
Primary outcome
Change in Borg Dyspnea Score
Time frame: The Peak Borg Dyspnea Score will be determined over 6 minutes of observation during the conduct of each 6-minute walk test. The 6-minute walk tests and assessments of the peak Borg Dyspnea Score will be recorded within 1 and 7 days of each other.
Change in peak Borg dyspnea score (morphine versus control)
1 secondary outcome
Change in 6-Minute Walk Distance
Time frame: The distance travelled during each 6 minute walk will be determined at completion of the 6-minute walk test. The distance travelled during the 6-minute walk test will be recorded within 1 and 7 days of each other.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Granton, MD, FRCPC principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Morphine Sulfate in people with Pulmonary Arterial Hypertension, run by John Granton at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Borg Dyspnea Score (time frame: The Peak Borg Dyspnea Score will be determined over 6 minutes of observation during the conduct of each 6-minute walk test. The 6-minute walk tests and assessments of the peak Borg Dyspnea Score will be recorded within 1 and 7 days of each other.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2018.