Cough, Idiopathic Pulmonary Fibrosis
Conditions
Keywords
idiopathic pulmonary fibrosis cough
Brief summary
Idiopathic Pulmonary Fibrosis (IPF) is a rapidly progressive lung disorder that is often associated with a chronic, intractable cough. The etiology of the cough associated with IPF is unclear but it is often so severe that it adversely effects the patient's quality of life. We propose that thalidomide specifically suppresses the cough associated with idiopathic pulmonary fibrosis via its anti-inflammatory properties, by suppressing the excessive functional up-regulation of sensory fibers with in the respiratory tract of patients with IPF. This study is a Phase III, double blinded, randomized, placebo controlled, crossover trial testing the efficacy of thalidomide in suppressing the chronic cough of IPF. The primary objective of this study is to determine the efficacy of thalidomide administered daily for 12 weeks to suppress the chronic cough in patients with idiopathic pulmonary fibrosis as measured by cough specific questionnaires, scales and improved quality of life.
Detailed description
This study is a Phase III, double blinded, randomized, placebo controlled, crossover trial testing the efficacy of thalidomide in suppressing the chronic cough of IPF. All subjects will be randomized to either begin the study receiving the active study drug - (thalidomide) or inactive drug (placebo). Study drug will be administered in escalating dose starting at 50 mg a day increasing to 100 mg a day if cough is still present after 2 weeks. Study drug will be taken by mouth at bedtime. Patients will remain on their initial treatment for 12 weeks. After 12 weeks of treatment, the subjects will be administered the Cough Specific Quality of Life Questionnaire (CQLQ), a visual cough analogue scale, and St. Georges Respiratory Questionnaire (SGRQ). In addition, investigators will collect the subjects cough diary. After 12 weeks of treatment all subjects will enter a 2 week wash-out phase in which all drugs will be discontinued. After the 2 week wash-out phase, all subjects will again be administered the Cough Specific Quality of Life Questionnaire (CQLQ), a visual cough analogue scale, and St. Georges Respiratory Questionnaire (SGRQ). In addition, investigators will collect the subjects cough diary. All subjects will then be crossed over to the other treatment arm for an additional 12 weeks of treatment. After the second 12 weeks of treatment, the subjects will be administered the Cough Specific Quality of Life Questionnaire (CQLQ), a visual cough analogue scale, and St. Georges Respiratory Questionnaire (SGRQ). In addition, investigators will collect the subjects cough diary.
Interventions
DRUGThalidomide
Thalidomide 50 - 100 mg by mouth daily
DRUGPlacebo
Placebo 50-100 mg by mouth per day
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Idiopathic pulmonary fibrosis for \>3 months \<5 years * High resolution CT scan of chest consistent with IPF within the previous 12 months * FVC \> 40% and \< 90% predicted, TLC \>40% \<80%, DLCo \>30% \<90% * Chronic Cough - cough \>8 weeks * Age \>50 * Non-child bearing potential
Exclusion criteria
* Pregnant or lactating women * Women of child bearing potential * Known etiology of lung fibrosis other than IPF * Significant respiratory toxin exposure * Collagen Vascular Disease * Use of narcotic anti-cough agent in last week * significant peripheral vascular disease or neuropathy * history of seizures * poorly controlled diabetes * allergy to thalidomide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire. | 6 months | The primary endpoint, suppression of cough was measured by the Cough Quality of Life Questionnaire (CQLQ) to measure the effect of interventions on cough-specific quality of life. CQLQ consist of 28 questions about cough and its effects using Likert-like 4-point scales, with lower scores indicating less effect of cough on health related quality of life. CQLQ scale ranges from 28 to 112 ( The lower the value, the higher the quality of life, 28 is considered the best). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | 6 months | The secondary endpoint, suppression of cough was measured by the visual analog scale of cough (VAS) was significantly lower during treatment with thalidomide than placebo. Secondary endpoints were Cough VAS - the visual analog scale of cough evaluates the severity of cough in patients with IPF. Visual analog scale of cough ranges from 0 to 100 (0 is considered the best). St. George Respiratory Questionnaire helps to evaluate cough-specific and respiratory quality of life in patients with IPF. St. George Respiratory Questionnaire score ranges from 0 to 100 (0 is considered the best). |
Countries
United States
Participant flow
Recruitment details
Consecutive eligible patients were recruited by the investigators from their clinics and through self-referral between February 2008 and March 2011. 98 persons contacted our study coordinator with queries about the trial, 22 from the Johns Hopkins Interstitial Lung Disease Clinic and 76 in response to the ClinicalTrials.gov Web site.
Pre-assignment details
One participant was excluded because of an FVC\>90% predicted
Participants by arm
| Arm | Count |
|---|---|
| Drug Thalidomide First, Then Placebo Drug thalidomide 50 - 100 mg daily in the first intervention period and placebo daily in the second intervention period (after washout period) | 13 |
| Placebo First, Then Thalidomide Drug Placebo was administered in the first intervention period and Thalidomide 50 - 100 mg daily in the second intervention period(After washout period) | 11 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (12 Weeks) | Adverse Event | 0 | 1 |
| First Intervention (12 Weeks) | Withdrawal by Subject | 1 | 0 |
| Second Intervention (12 Weeks) | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo First, Then Thalidomide Drug | Drug Thalidomide First, Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 13 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 65.55 years STANDARD_DEVIATION 7.38 | 70.5 years STANDARD_DEVIATION 7.11 | 67.8 years STANDARD_DEVIATION 7.8 |
| Region of Enrollment United States | 11 participants | 13 participants | 24 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 23 | 1 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire.
The primary endpoint, suppression of cough was measured by the Cough Quality of Life Questionnaire (CQLQ) to measure the effect of interventions on cough-specific quality of life. CQLQ consist of 28 questions about cough and its effects using Likert-like 4-point scales, with lower scores indicating less effect of cough on health related quality of life. CQLQ scale ranges from 28 to 112 ( The lower the value, the higher the quality of life, 28 is considered the best).
Time frame: 6 months
Population: All participants who received the interventions and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire. | 47.3 units on a scale | Standard Deviation 13.7 |
| Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire. | 55.2 units on a scale | Standard Deviation 14.4 |
| Arm Placebo 1st, Thalidomide 2nd (Intervention Placebo) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire. | 61.6 units on a scale | Standard Deviation 11.9 |
| Arm Placebo 1st, Thalidomide 2nd (Intervention Thalidomide) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire. | 44.5 units on a scale | Standard Deviation 12.5 |
p-value: 0.001Mixed Models Analysis
Secondary
Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire.
The secondary endpoint, suppression of cough was measured by the visual analog scale of cough (VAS) was significantly lower during treatment with thalidomide than placebo. Secondary endpoints were Cough VAS - the visual analog scale of cough evaluates the severity of cough in patients with IPF. Visual analog scale of cough ranges from 0 to 100 (0 is considered the best). St. George Respiratory Questionnaire helps to evaluate cough-specific and respiratory quality of life in patients with IPF. St. George Respiratory Questionnaire score ranges from 0 to 100 (0 is considered the best).
Time frame: 6 months
Population: All participants who received the interventions and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Quality of life (SGRQ Score) | 46.4 units on a scale | Standard Deviation 19.4 |
| Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Severity of cough (VAS Score) | 30.3 units on a scale | Standard Deviation 28.5 |
| Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Severity of cough (VAS Score) | 65.9 units on a scale | Standard Deviation 23.3 |
| Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Quality of life (SGRQ Score) | 54.7 units on a scale | Standard Deviation 16.9 |
| Arm Placebo 1st, Thalidomide 2nd (Intervention Placebo) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Severity of cough (VAS Score) | 68 units on a scale | Standard Deviation 26.8 |
| Arm Placebo 1st, Thalidomide 2nd (Intervention Placebo) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Quality of life (SGRQ Score) | 58.8 units on a scale | Standard Deviation 13.3 |
| Arm Placebo 1st, Thalidomide 2nd (Intervention Thalidomide) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Quality of life (SGRQ Score) | 40.7 units on a scale | Standard Deviation 9.5 |
| Arm Placebo 1st, Thalidomide 2nd (Intervention Thalidomide) | Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire. | Severity of cough (VAS Score) | 17.8 units on a scale | Standard Deviation 9.9 |
p-value: 0.0001Mixed Models Analysis