Trial Outcomes & Findings for Pioglitazone for Lung Cancer Chemoprevention (NCT NCT00780234)
NCT ID: NCT00780234
Last Updated: 2019-04-11
Results Overview
Biopsies were classified into one of the following 8 World Health Organization defined categories to classify the endobronchial lesion and assign a score according to the following scale: 1 = normal bronchial epithelium; 2 = reserve cell hyperplasia; 3 = squamous metaplasia without atypia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ (CIS); and 8 = invasive carcinoma. 1 represents the best outcome and 8 represents the worst outcome.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
92 participants
Primary outcome timeframe
6 months
Results posted on
2019-04-11
Participant Flow
243 subjects were consented to provide a pre-screening sputum cytology specimen, and of those, 92 enrolled onto full trial.
243 subjects were consented to provide a pre-screening sputum cytology specimen, and of those, 92 enrolled onto full trial.
Participant milestones
| Measure |
Arm 1: Pioglitazone
Current or former smokers receive 6 months of treatment with pioglitazone.
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light.
quantitative high resolution CT scan: High resolution chest CT scan
PIOGLITAZONE VS. PLACEBO 30 mg: Patients will be randomized to receive either pioglitazone or placebo. Pioglitazone hydrochloride, a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator- activated receptor-gamma agonist.
|
Arm 2: Placebo
Current or former smokers receive 6 months of treatment with placebo
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
45
|
|
Overall Study
COMPLETED
|
39
|
37
|
|
Overall Study
NOT COMPLETED
|
8
|
8
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pioglitazone for Lung Cancer Chemoprevention
Baseline characteristics by cohort
| Measure |
Arm 1: Pioglitazone
n=47 Participants
Current or former smokers receive 6 months of treatment with pioglitazone
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
PIOGLITAZONE VS. PLACEBO 30 mg: Patients will be randomized to receive either pioglitazone or placebo. Pioglitazone hydrochloride, a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator-
activated receptor-gamma agonist. It is FDA approved for the treatment of Type II diabetes. It has been previously administered to non-diabetic subjects. The most common side effect of pioglitazone is fluid retention and modest weight gain. There is a potential risk that pioglitazone may cause an elevation in liver enzymes and more serious hepatotoxicity (rare). There is risk of edema and weight gain associated with pioglitazone therapy. 5% experienced peripheral edema in clinical trials.
|
Arm 2: Placebo
n=45 Participants
Current or former smokers receive 6 months of treatment with placebo
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.6 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
62.6 years
STANDARD_DEVIATION 8.2 • n=7 Participants
|
60.5 years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity/Race · Hispanic
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity/Race · Non-Hispanic White
|
41 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity/Race · Non-Hispanic Black
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity/Race · Non-Hispanic American Indian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Although 76 subjects had a 6-month bronchoscopy (39 pioglitazone, 37 placebo), only 64 subjects (34 pioglitazone, 30 placebo) had matched biopsy pairs with non-normal tissue at baseline. Of these 64, 29 were former smokers (15 pioglitazone, 14 placebo), which was the a priori group for the primary analysis.
Biopsies were classified into one of the following 8 World Health Organization defined categories to classify the endobronchial lesion and assign a score according to the following scale: 1 = normal bronchial epithelium; 2 = reserve cell hyperplasia; 3 = squamous metaplasia without atypia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ (CIS); and 8 = invasive carcinoma. 1 represents the best outcome and 8 represents the worst outcome.
Outcome measures
| Measure |
Arm 1: Pioglitazone
n=15 Participants
Current or former smokers receive 6 months of treatment with pioglitazone
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
PIOGLITAZONE VS. PLACEBO 30 mg: Patients will be randomized to receive either pioglitazone or placebo. Pioglitazone hydrochloride, a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator-
activated receptor-gamma agonist. It is FDA approved for the treatment of Type II diabetes. It has been previously administered to non-diabetic subjects. The most common side effect of pioglitazone is fluid retention and modest weight gain. There is a potential risk that pioglitazone may cause an elevation in liver enzymes and more serious hepatotoxicity (rare). There is risk of edema and weight gain associated with pioglitazone therapy. 5% experienced peripheral edema in clinical trials.
|
Arm 2: Placebo
n=14 Participants
Current or former smokers receive 6 months of treatment with placebo
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
|
|---|---|---|
|
6-month Histology Score
|
3.07 Units on a scale
Standard Deviation 2.02
|
3.71 Units on a scale
Standard Deviation 2.02
|
Adverse Events
Arm 1: Pioglitazone
Serious events: 3 serious events
Other events: 44 other events
Deaths: 1 deaths
Arm 2: Placebo
Serious events: 5 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1: Pioglitazone
n=47 participants at risk
Current or former smokers receive 6 months of treatment with pioglitazone
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
PIOGLITAZONE VS. PLACEBO 30 mg: Patients will be randomized to receive either pioglitazone or placebo. Pioglitazone hydrochloride, a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator-
activated receptor-gamma agonist. It is FDA approved for the treatment of Type II diabetes. It has been previously administered to non-diabetic subjects. The most common side effect of pioglitazone is fluid retention and modest weight gain. There is a potential risk that pioglitazone may cause an elevation in liver enzymes and more serious hepatotoxicity (rare). There is risk of edema and weight gain associated with pioglitazone therapy. 5% experienced peripheral edema in clinical trials.
|
Arm 2: Placebo
n=45 participants at risk
Current or former smokers receive 6 months of treatment with placebo
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
|
|---|---|---|
|
Metabolism and nutrition disorders
Alcohol Intolerance
|
2.1%
1/47 • Number of events 1 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
|
Cardiac disorders
Atrial Fibrillation
|
2.1%
1/47 • Number of events 1 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial Infection
|
2.1%
1/47 • Number of events 1 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
|
Psychiatric disorders
Depression
|
2.1%
1/47 • Number of events 1 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
|
General disorders
Edema Limbs
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
General disorders
Fever
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Cardiac disorders
Heart Failure
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Cardiac disorders
Hypertension
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic Pain
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/47 • 4 years, 11 months
|
4.4%
2/45 • Number of events 2 • 4 years, 11 months
|
|
Skin and subcutaneous tissue disorders
Skin Infection
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Psychiatric disorders
Suicidal Ideation
|
2.1%
1/47 • Number of events 1 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
|
Nervous system disorders
Syncope
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Investigations
Weight Gain
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/47 • 4 years, 11 months
|
2.2%
1/45 • Number of events 1 • 4 years, 11 months
|
Other adverse events
| Measure |
Arm 1: Pioglitazone
n=47 participants at risk
Current or former smokers receive 6 months of treatment with pioglitazone
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
PIOGLITAZONE VS. PLACEBO 30 mg: Patients will be randomized to receive either pioglitazone or placebo. Pioglitazone hydrochloride, a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator-
activated receptor-gamma agonist. It is FDA approved for the treatment of Type II diabetes. It has been previously administered to non-diabetic subjects. The most common side effect of pioglitazone is fluid retention and modest weight gain. There is a potential risk that pioglitazone may cause an elevation in liver enzymes and more serious hepatotoxicity (rare). There is risk of edema and weight gain associated with pioglitazone therapy. 5% experienced peripheral edema in clinical trials.
|
Arm 2: Placebo
n=45 participants at risk
Current or former smokers receive 6 months of treatment with placebo
fluorescence bronchoscopy: examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
quantitative high resolution CT scan: High resolution CT scan of the chest
|
|---|---|---|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
46.8%
22/47 • 4 years, 11 months
|
62.2%
28/45 • 4 years, 11 months
|
|
Cardiac disorders
Hypertension
|
51.1%
24/47 • 4 years, 11 months
|
46.7%
21/45 • 4 years, 11 months
|
|
Investigations
Weight Gain
|
42.6%
20/47 • 4 years, 11 months
|
22.2%
10/45 • 4 years, 11 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
27.7%
13/47 • 4 years, 11 months
|
20.0%
9/45 • 4 years, 11 months
|
|
Blood and lymphatic system disorders
Anemia
|
23.4%
11/47 • 4 years, 11 months
|
20.0%
9/45 • 4 years, 11 months
|
|
Investigations
Aspartate Aminotransferase Increased
|
23.4%
11/47 • 4 years, 11 months
|
17.8%
8/45 • 4 years, 11 months
|
|
General disorders
Edema Limbs
|
12.8%
6/47 • 4 years, 11 months
|
24.4%
11/45 • 4 years, 11 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
8.5%
4/47 • 4 years, 11 months
|
26.7%
12/45 • 4 years, 11 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
17.0%
8/47 • 4 years, 11 months
|
6.7%
3/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial Infection
|
12.8%
6/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
Investigations
GGT Increased
|
8.5%
4/47 • 4 years, 11 months
|
15.6%
7/45 • 4 years, 11 months
|
|
Investigations
Alanine Aminotransferase Increased
|
12.8%
6/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.6%
5/47 • 4 years, 11 months
|
11.1%
5/45 • 4 years, 11 months
|
|
Investigations
White Blood Cell Decreased
|
12.8%
6/47 • 4 years, 11 months
|
6.7%
3/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
10.6%
5/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
Cardiac disorders
Sinus Tachycardia
|
10.6%
5/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.3%
2/47 • 4 years, 11 months
|
11.1%
5/45 • 4 years, 11 months
|
|
General disorders
Non-Cardiac Chest Pain
|
8.5%
4/47 • 4 years, 11 months
|
4.4%
2/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
8.5%
4/47 • 4 years, 11 months
|
4.4%
2/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.3%
2/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
General disorders
Fever
|
4.3%
2/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
Investigations
Platelet Count Decreased
|
4.3%
2/47 • 4 years, 11 months
|
8.9%
4/45 • 4 years, 11 months
|
|
Gastrointestinal disorders
Vomiting
|
6.4%
3/47 • 4 years, 11 months
|
4.4%
2/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.4%
3/47 • 4 years, 11 months
|
4.4%
2/45 • 4 years, 11 months
|
|
Investigations
Alkaline Phosphatase Increased
|
4.3%
2/47 • 4 years, 11 months
|
6.7%
3/45 • 4 years, 11 months
|
|
General disorders
Fatigue
|
4.3%
2/47 • 4 years, 11 months
|
6.7%
3/45 • 4 years, 11 months
|
|
Nervous system disorders
Dizziness
|
8.5%
4/47 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis
|
6.4%
3/47 • 4 years, 11 months
|
2.2%
1/45 • 4 years, 11 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.4%
3/47 • 4 years, 11 months
|
2.2%
1/45 • 4 years, 11 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
2.1%
1/47 • 4 years, 11 months
|
6.7%
3/45 • 4 years, 11 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
6.4%
3/47 • 4 years, 11 months
|
0.00%
0/45 • 4 years, 11 months
|
Additional Information
Robert L. Keith, MD
Rocky Mountain Regional VA Medical Center
Phone: 720-857-5120
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place