Trial Outcomes & Findings for Morphine Sulfate/Placebo for the Treatment of PulmonAry Fibrosis Cough (NCT NCT04429516)

NCT ID: NCT04429516

Last Updated: 2026-05-07

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

44 participants

Primary outcome timeframe

from baseline as assessed by objective digital cough monitoring at Day 14 of treatment

Results posted on

2026-05-07

Participant Flow

47 individuals assessed for eligibility 3 excluded 44 enrolled and randomly assigned

out if the 47 individuals assessed for eligibility 3 did not meet the inclusion criteria; 44 enrolled and randomly assigned and 1 withdrew before treatment

Participant milestones

Participant milestones
Measure
Morphine Sulfate Then Placebo
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period. Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Placebo Then Morphine Sulfate
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily Patients will then crossover after a 7 day wash out period. Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days.
Period 1 - Randomisation
STARTED
21
22
Period 1 - Randomisation
COMPLETED
21
22
Period 1 - Randomisation
NOT COMPLETED
0
0
Period 2 - CROSS-OVER
STARTED
21
22
Period 2 - CROSS-OVER
COMPLETED
17
20
Period 2 - CROSS-OVER
NOT COMPLETED
4
2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Morphine Sulfate/Placebo for the Treatment of PulmonAry Fibrosis Cough

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Morphine Sulfate Then Placebo
n=21 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period. Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Placebo Then Morphine Sulfate
n=22 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily. Patients will then crossover after a 7 day wash out period. Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days.
Total
n=43 Participants
Total of all reporting groups
Race/Ethnicity, Customized
Indian
2 Participants
n=54 Participants
1 Participants
n=60 Participants
3 Participants
n=114 Participants
Age, Customized
Age (years)
71 years
STANDARD_DEVIATION 7.2 • n=54 Participants
71 years
STANDARD_DEVIATION 7.5 • n=60 Participants
71 years
STANDARD_DEVIATION 7.4 • n=114 Participants
Sex: Female, Male
Female
6 Participants
n=54 Participants
6 Participants
n=60 Participants
12 Participants
n=114 Participants
Sex: Female, Male
Male
15 Participants
n=54 Participants
16 Participants
n=60 Participants
31 Participants
n=114 Participants
Race/Ethnicity, Customized
Caucasian
19 Participants
n=54 Participants
21 Participants
n=60 Participants
40 Participants
n=114 Participants

PRIMARY outcome

Timeframe: from baseline as assessed by objective digital cough monitoring at Day 14 of treatment

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
The Percent Change in Daytime Cough Frequency (Coughs Per Hour)
-40.8 % change
Interval -54.2 to -23.6
-4.3 % change
Interval -21.8 to 17.0

SECONDARY outcome

Timeframe: At Day 0, Day 14

Population: Intention to treat

Living with Idiopathic Pulmonary Fibrosis (L-IPF): Developing a Patient-Reported Symptom and Impact Questionnaire to Assess Health-Related Quality of Life in IPF; on a scale between 0 to 4, where 0 is Not at all and 4 is Extremlly. QoL scores were measured at baseline and day 14. A single estimate was reported which is the mean change from baseline

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Health-related Quality of Life Scores (Living With Idiopathic Pulmonary Fibrosis Questionnaire)
-5.2 score on a scale
Interval -9.9 to -0.4
-1.7 score on a scale
Interval -5.5 to 2.1

SECONDARY outcome

Timeframe: At Day 0, Day 14

Population: intention to treat

HADS - Hospital Anxiety and Depression Scale (Scoring 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case). QoL scores were measured at baseline and day 14. A single estimate was reported which is the mean change from baseline

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Health-related Quality of Life Scores (HADS- Hospital Anxiety and Depression Scale)
Anxiety
0.1 score on a scale
Interval -0.1 to 0.2
0.0 score on a scale
Interval -0.1 to 0.2
Change From Baseline in Health-related Quality of Life Scores (HADS- Hospital Anxiety and Depression Scale)
Depression
0.0 score on a scale
Interval 0.0 to 0.0
-0.1 score on a scale
Interval -0.2 to 0.1

SECONDARY outcome

Timeframe: At Day 0, Day 14

Population: intention to treat

The KBILD is a self-completed health status questionnaire that comprises 15 items and a seven-point Likert response scale. It has three domains: psychological, breathlessness and activities and chest symptoms. The KBILD score ranges are 0-100; 100 represents best health status. QoL scores were measured at baseline and day 14. A single estimate was reported which is the mean change from baseline

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Health-related Quality of Life Scores (K-BILD - King's Brief Interstitial Lung Disease Questionnaire)
-0.2 score on a scale
Interval -0.6 to 0.2
0.2 score on a scale
Interval -0.5 to 0.9

SECONDARY outcome

Timeframe: At Day 0, Day 14

Population: intention to treat

The Leicester Cough Questionnaire comprises of 19 questions. Score ranges from 3 to 21 with higher values indicating a better QoL. 8 of the questions assess the physical cough domain, 7 items assess the psychological impact of cough, and 4 questions assess the social impact of cough. QoL scores were measured at baseline and day 14. A single estimate was reported which is the mean change from baseline

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Self-reported Cough (Leicester Cough Questionnaire (LCQ)
1.8 score on a scale
Interval 0.9 to 2.8
0.6 score on a scale
Interval -0.2 to 1.3

SECONDARY outcome

Timeframe: At Day 0, Day 14

Population: intention to treat

VAS - The cough visual analogue scale (VAS) represents a simple instrument, using a 100 mm linear scale where patient can indicate the severity of their cough between the two extremes: zero is no cough while 100 mm is the worst cough imaginable. QoL scores were measured at baseline and day 14. A single estimate was reported which is the mean change from baseline

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Self-reported Cough - Visual Analogue Scale (VAS)
-16.1 score on a scale
Interval -22.3 to -9.9
-0.4 score on a scale
Interval -5.8 to 4.9

SECONDARY outcome

Timeframe: At Day 0, Day 14

Population: intention to treat

D-12 consists of 12 descriptor items on a scale of none (0), mild (1), moderate (2), or severe (3). It provides an overall score for breathlessness severity that incorporates seven physical items and five affective items. The range of scores is between 0 and 36 with higher score representing greater levels of dyspnoea. QoL scores were measured at baseline and day 14. A single estimate was reported which is the mean change from baseline

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Dyspnoea (Dyspnoea 12)
-0.1 score on a scale
Interval -1.9 to 1.6
0.9 score on a scale
Interval -0.5 to 2.2

SECONDARY outcome

Timeframe: At Day 14 and Day 36

Population: intention to treat

It provides a brief, stand-alone assessment of treatment effect on cough, breathlessness and overall quality of live on a scale of: worse, same and better.

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=41 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Change From Baseline in Global Impression of Change in Quality of Life, Cough and Breathlessness.
Cough worse
8 participants
15 participants
Change From Baseline in Global Impression of Change in Quality of Life, Cough and Breathlessness.
Dyspnoea worse
6 participants
9 participants
Change From Baseline in Global Impression of Change in Quality of Life, Cough and Breathlessness.
Overall quality of life worse
5 participants
4 participants

SECONDARY outcome

Timeframe: Comparison made between pre-treatment and at follow up visit in both the first and then the crossover arms of the study: Day 0, Day 14, Day 22 and Day 36

Population: intention to treat

Proportion of responders with a minimum of 20% decrease from baseline at the end of treatment in 24-hour average cough count.

Outcome measures

Outcome measures
Measure
Morphine Sulfate
n=43 Participants
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=39 Participants
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily
Proportion of Responders With a Minimum of 20% Decrease From Baseline at the End of Treatment in 24-hour Average Cough Count.
25 participants
14 participants

Adverse Events

Morphine Sulfate

Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 6 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Morphine Sulfate
n=43 participants at risk
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=42 participants at risk
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily. Patients will then crossover after a 7 day wash out period
Respiratory, thoracic and mediastinal disorders
Lung infection
0.00%
0/43 • From baseline until event resolution, an average of 30 days
AEs were summarised for Morphine and Placebo arm separately. 43 people received Morphine and 42 received Placebo
2.4%
1/42 • Number of events 1 • From baseline until event resolution, an average of 30 days
AEs were summarised for Morphine and Placebo arm separately. 43 people received Morphine and 42 received Placebo

Other adverse events

Other adverse events
Measure
Morphine Sulfate
n=43 participants at risk
Morphine Sulfate: over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.
Placebo
n=42 participants at risk
Placebo oral tablet: capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily. Patients will then crossover after a 7 day wash out period
Respiratory, thoracic and mediastinal disorders
Lung infection
39.5%
17/43 • Number of events 17 • From baseline until event resolution, an average of 30 days
AEs were summarised for Morphine and Placebo arm separately. 43 people received Morphine and 42 received Placebo
14.3%
6/42 • Number of events 6 • From baseline until event resolution, an average of 30 days
AEs were summarised for Morphine and Placebo arm separately. 43 people received Morphine and 42 received Placebo

Additional Information

Professor

Royal Brompton and Harefield Hospitals

Phone: +44(0)207 352 8121

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place