Effect of Morphine on Dyspnea and 6-Minute Walk Distance in Pulmonary Arterial Hypertension

NCT03401476 | Unknown Phase 2

• 1 other identifier: MorPHine
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in Borg Dyspnea Score

  Change in peak Borg dyspnea score (morphine versus control)

  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

  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.

Study Arms (2)

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.

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.

Drug: Morphine Sulfate

Interventions

Morphine Sulfate DRUG

Morphine Sulfate Tablets

Also known as: Statex

Morphine sulfate - Visit 1; Morphine sulfate - Visit 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• John Granton: lead

Study Sites (1)

University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Morphine

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• John Granton, MD, FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2017
• First Posted: January 17, 2018
• Study Start: May 8, 2017
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2019
• Last Updated: January 18, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)