Pulmonary Arterial Hypertension
Conditions
Brief summary
To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.
Interventions
DRUGSildenafil citrate
oral, 20 mg, tid
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with PAH (i.e. IPAH or secondary to connective tissue disease or with surgical repair of ASD, VSD, PDA, aorto-pulmonary window) whose baseline six minute walk test distance is \>/= 100 m and \</= 450 m. * Subjects with a mean pulmonary artery pressure of \>/= 25 mmHg and a pulmonary artery wedge pressure of \</= 15 mmHg at rest via right heart catheterization performed within 12 weeks prior to randomization.
Exclusion criteria
* Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis. * Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of bosentan or prostacyclin (3 months).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 | Baseline and Week 12 | 6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 | Baseline and Week 12 | mPAP was measured using a pressure transducer positioned at the mid-axillary line. |
| Number of Participants With Clinical Worsening | Baseline through Week 12 | Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated. |
| Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Baseline and Week 12 | Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity). |
| Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12 | Baseline and Week 12 | BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH. |
| Change From Baseline in Pro-BNP at Week 12 | Baseline and Week 12 | Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH. |
| Change From Baseline in TAPSE Measurement at Week 12 | Baseline and Week 12 | Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction. The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis. |
| Change From Baseline in BORG Dyspnoea Score at Week 12 | Baseline and Week 12 | BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight \[just noticeable\]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe \[almost maximum\] and 10 (maximum). |
Countries
Belgium, Brazil, Bulgaria, China, Greece, India, Italy, Latvia, Malaysia, Netherlands, Philippines, Poland, Romania, Russia, Thailand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil 1 mg Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. | 41 |
| Sildenafil 5 mg Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. | 43 |
| Sildenafil 20 mg Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase). | 45 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double Blind Phase | Adverse Event | 1 | 1 | 3 |
| Double Blind Phase | Death | 1 | 0 | 0 |
| Double Blind Phase | No longer willing to participate | 2 | 1 | 1 |
| Double Blind Phase | Not treated | 1 | 0 | 0 |
| Double Blind Phase | Other | 0 | 2 | 0 |
| Double Blind Phase | Study terminated by sponsor | 1 | 1 | 2 |
| Open Label Phase | Lost to Follow-up | 1 | 0 | 1 |
| Open Label Phase | No longer willing to participate | 0 | 1 | 1 |
| Open Label Phase | Other | 3 | 1 | 1 |
| Open Label Phase | Protocol Violation | 1 | 0 | 0 |
| Open Label Phase | Study terminated by sponsor | 4 | 5 | 4 |
Baseline characteristics
| Characteristic | Sildenafil 1 mg | Sildenafil 5 mg | Sildenafil 20 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 16.5 | 44.4 Years STANDARD_DEVIATION 17.4 | 46.4 Years STANDARD_DEVIATION 17.7 | 44.5 Years STANDARD_DEVIATION 17.2 |
| Sex: Female, Male Female | 28 Participants | 33 Participants | 26 Participants | 87 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 19 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 41 | 1 / 43 | 0 / 45 |
| other Total, other adverse events | 21 / 41 | 22 / 43 | 22 / 45 |
| serious Total, serious adverse events | 6 / 41 | 3 / 43 | 5 / 45 |
Outcome results
Primary
Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12
6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.
Time frame: Baseline and Week 12
Population: Intention to Treat (ITT population) included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, last observation carried forward (LOCF) method of imputation was used.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil 1 mg | Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 | 14.21 Meters |
| Sildenafil 5 mg | Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 | 40.75 Meters |
| Sildenafil 20 mg | Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 | 38.36 Meters |
Comparison: An analysis of variance (ANOVA) model followed by the Williams trend test (one-sided, at the 2.5% level of significance) was used. The Williams trend test firstly determined if there was a significant downward trend in response for the descending doses, and then subsequently determined the highest dose that was statistically inferior to 20 mg (known to be an effective dose of sildenafil). A corresponding 97.5% lower confidence limit for the difference was presented.p-value: 0.011ANOVA
Comparison: ANOVA model followed by the Williams trend test (one-sided, at the 2.5% level of significance) was used. The Williams trend test firstly determined if there was a significant downward trend in response for the descending doses, and then subsequently determined the highest dose that was statistically inferior to 20 mg (known to be an effective dose of sildenafil). A corresponding 97.5% lower confidence limit for the difference was presented.p-value: 0.545ANOVA
Secondary
Change From Baseline in BORG Dyspnoea Score at Week 12
BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight \[just noticeable\]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe \[almost maximum\] and 10 (maximum).
Time frame: Baseline and Week 12
Population: ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil 1 mg | Change From Baseline in BORG Dyspnoea Score at Week 12 | -0.28 Units on a scale |
| Sildenafil 5 mg | Change From Baseline in BORG Dyspnoea Score at Week 12 | -0.89 Units on a scale |
| Sildenafil 20 mg | Change From Baseline in BORG Dyspnoea Score at Week 12 | -0.43 Units on a scale |
Comparison: A stratified Wilcoxon test (Van-Elteren) was used. The stratified median difference and corresponding two-sided 95% CI (calculated using the Hodges-Lehmann estimator) was presented along with the p-value for the test.p-value: 0.38295% CI: [-1, 0]Wilcoxon (Van-Elteren)
Comparison: A stratified Wilcoxon test (Van-Elteren) was used. The stratified median difference and corresponding two-sided 95% CI (calculated using the Hodges-Lehmann estimator) was presented along with the p-value for the test.p-value: 0.14195% CI: [0, 1]Wilcoxon (Van-Elteren)
Secondary
Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12
BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.
Time frame: Baseline and Week 12
Population: ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil 1 mg | Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12 | -6.28 pg/mL |
| Sildenafil 5 mg | Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12 | -53.46 pg/mL |
| Sildenafil 20 mg | Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12 | -97.42 pg/mL |
Comparison: ANCOVA method was used with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.p-value: 0.00595% CI: [-177.44, -32.16]ANCOVA
Comparison: ANCOVA method was used with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.p-value: 0.49695% CI: [-97.5, 47.5]ANCOVA
Secondary
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12
mPAP was measured using a pressure transducer positioned at the mid-axillary line.
Time frame: Baseline and Week 12
Population: ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil 1 mg | Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 | -1.73 mmHg |
| Sildenafil 5 mg | Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 | -3.44 mmHg |
| Sildenafil 20 mg | Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 | -3.29 mmHg |
Comparison: The analysis of change from baseline in week 12 mean PAP used Analysis of Covariance (ANCOVA), with etiology and baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.p-value: 0.27895% CI: [-7.07, 2.05]ANCOVA
Comparison: The analysis of change from baseline in week 12 mean PAP used ANCOVA, with etiology and baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.p-value: 0.84695% CI: [-4.98, 4.09]ANCOVA
Secondary
Change From Baseline in Pro-BNP at Week 12
Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.
Time frame: Baseline and Week 12
Population: ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil 1 mg | Change From Baseline in Pro-BNP at Week 12 | -111.53 pg/mL |
| Sildenafil 5 mg | Change From Baseline in Pro-BNP at Week 12 | -306.76 pg/mL |
| Sildenafil 20 mg | Change From Baseline in Pro-BNP at Week 12 | -428.54 pg/mL |
Comparison: ANCOVA method was used with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.p-value: 0.00995% CI: [-807.53, -116.71]ANCOVA
Comparison: ANCOVA method was used with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.p-value: 0.41495% CI: [-483.48, 200.58]ANCOVA
Secondary
Change From Baseline in TAPSE Measurement at Week 12
Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction. The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.
Time frame: Baseline and Week 12
Population: ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil 1 mg | Change From Baseline in TAPSE Measurement at Week 12 | 0.08 cm |
| Sildenafil 5 mg | Change From Baseline in TAPSE Measurement at Week 12 | 0.17 cm |
| Sildenafil 20 mg | Change From Baseline in TAPSE Measurement at Week 12 | -0.02 cm |
Comparison: ANCOVA method was used with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.p-value: 0.8995% CI: [-0.17, 0.15]ANCOVA
Comparison: ANCOVA method was used with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.p-value: 0.12495% CI: [-0.29, 0.04]ANCOVA
Secondary
Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12
Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).
Time frame: Baseline and Week 12
Population: ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sildenafil 1 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Worsened 2 Classes | 0 Participants |
| Sildenafil 1 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Worsened 1 Class | 1 Participants |
| Sildenafil 1 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | No Change | 35 Participants |
| Sildenafil 1 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Improved 1 Class | 4 Participants |
| Sildenafil 1 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Improved 2 Classes | 1 Participants |
| Sildenafil 1 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Missing | 0 Participants |
| Sildenafil 5 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Worsened 1 Class | 3 Participants |
| Sildenafil 5 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Improved 1 Class | 10 Participants |
| Sildenafil 5 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Missing | 3 Participants |
| Sildenafil 5 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Worsened 2 Classes | 0 Participants |
| Sildenafil 5 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | No Change | 27 Participants |
| Sildenafil 5 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Improved 2 Classes | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Worsened 2 Classes | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Improved 2 Classes | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | No Change | 35 Participants |
| Sildenafil 20 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Missing | 2 Participants |
| Sildenafil 20 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Worsened 1 Class | 2 Participants |
| Sildenafil 20 mg | Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 | Improved 1 Class | 6 Participants |
Comparison: The analysis of the week 12 PAH functional class was done with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates.The odds ratio and corresponding two-sided 95% CI for the odds ratio for the treatment comparisons was presented along with the p-value for the tests.p-value: 0.44895% CI: [0.5, 4.78]Regression, Logistic
Comparison: The analysis of the week 12 PAH functional class was done with etiology, baseline walking distance category (\<325m or \>=325m) and baseline score as the covariates.The odds ratio and corresponding two-sided 95% CI for the odds ratio for the treatment comparisons was presented along with the p-value for the tests.p-value: 0.89795% CI: [0.35, 3.32]Regression, Logistic
Secondary
Number of Participants With Clinical Worsening
Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.
Time frame: Baseline through Week 12
Population: ITT population for clinical worsening included all participants who had been randomized to study treatment and received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sildenafil 1 mg | Number of Participants With Clinical Worsening | hospitalisation due to pulmonary hypertension | 1 Participants |
| Sildenafil 1 mg | Number of Participants With Clinical Worsening | lung transplantation | 0 Participants |
| Sildenafil 1 mg | Number of Participants With Clinical Worsening | PAH deterioration requiring therapy | 0 Participants |
| Sildenafil 1 mg | Number of Participants With Clinical Worsening | receptor antagonist therapy | 0 Participants |
| Sildenafil 1 mg | Number of Participants With Clinical Worsening | death | 1 Participants |
| Sildenafil 5 mg | Number of Participants With Clinical Worsening | death | 1 Participants |
| Sildenafil 5 mg | Number of Participants With Clinical Worsening | receptor antagonist therapy | 1 Participants |
| Sildenafil 5 mg | Number of Participants With Clinical Worsening | lung transplantation | 0 Participants |
| Sildenafil 5 mg | Number of Participants With Clinical Worsening | PAH deterioration requiring therapy | 0 Participants |
| Sildenafil 5 mg | Number of Participants With Clinical Worsening | hospitalisation due to pulmonary hypertension | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Clinical Worsening | PAH deterioration requiring therapy | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Clinical Worsening | hospitalisation due to pulmonary hypertension | 2 Participants |
| Sildenafil 20 mg | Number of Participants With Clinical Worsening | receptor antagonist therapy | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Clinical Worsening | death | 0 Participants |
| Sildenafil 20 mg | Number of Participants With Clinical Worsening | lung transplantation | 0 Participants |