Intermittent Claudication Fontaine Stage II PAOD, Stage II Peripheral Arterial Occlusive Disease
Conditions
Keywords
Alprostadil, Prostaglandin E1, Prostavasin®, PAOD
Brief summary
Investigate, under outpatient conditions, both the effect of 4 weeks of daily treatment with Prostaglandin E1 and that of 4 weeks of interval treatment (two infusions per week) on the pain-free walking distance in patients with Intermittent Claudication.
Interventions
4-week Daily Treatment Period 1: 4 weeks of 1 x daily intravenous infusion of 3 ampoules (20 µg) of Prostaglandin E1 (total 60 µg) in 50 - 250 ml physiological saline solution over 2 hours. 4-week Interval Treatment Period 2: 4 weeks of 2 x weekly intravenous infusion of 3 ampoules (20 µg) of Prostaglandin E1 (total 60 µg) in 50 - 250 ml physiological saline solution over 2 hours.
DRUGPentoxifylline
4-week Daily Treatment Period 1: 4 weeks of 2 x daily (including weekends) 600 mg Pentoxifylline tablets. 4-week Interval Treatment Period 2: 4 weeks of 2 x daily (including weekends) 600 mg Pentoxifylline tablets.
DRUGPlacebo to Pentoxifylline oral
4-week Daily Treatment Period 1: 4 weeks of 2 x daily (including weekends) matching Placebo to Pentoxifylline tablets. 4-week Interval Treatment Period 2: 4 weeks of 2 x daily (including weekends) matching Placebo to Pentoxifylline tablets.
DRUGPlacebo to Alprostadil (Prostaglandin E1) intravenous
4-week Daily Treatment Period 1: 4 weeks of 1 x daily intravenous infusion of Placebo in 50 - 250 ml physiological saline solution over 2 hours. 4-week Interval Treatment Period 2: 4 weeks of 2 x weekly intravenous infusion of Placebo in 50 - 250 ml physiological saline solution over 2 hours.
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with Peripheral Arterial Occlusive Disease (PAOD) of the lower extremity in Fontaine stage II * Maximum walking distance on the treadmill (12 %, 3 km/h) between 30 and 150 m * Stable Intermittent Claudication of at least 6 months standing with no acute shortening of walking distance over the past 3 months * Stenoses or occlusions below the Femoral Bifurcation (above-knee or below-knee type) confirmed by duplex US or angiography * Ankle/brachial index ≤ 0.90 with a decrease in systolic ankle pressure of ≥ 10 % after maximum loading (maximum walking distance on the treadmill at 3 km/h, 12 %) * The patient is physically and mentally capable of participating in the trial * Patient age \> 40 years, male and female * Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent * Patient is willing and able to comply with all trial requirements
Exclusion criteria
* Surgical or other interventional measures performed on the affected extremity and Prostaglandin treatment within the 6 months immediately prior to the trial * Rest pain and Necroses * Systolic ankle pressure less than 50 mmHg * Change in maximum walking distance during the one-week Run-in Phase of more than ± 25 % of Baseline * Successful physical walking training within the 6 months immediately prior to the trial * Inflammatory vascular diseases * Polyneuropathy in Diabetes Mellitus * Diseases limiting walking distance (Arthrosis, inflammatory diseases of the joints, neurological disease, diseases of the Vertebral Column, cardiopulmonary diseases) * History of Pulmonary Oedema * Myocardial infarction within the past 6 months * Pregnancy or nursing * Known hypersensitivity to any components of the trial medication or comparative drug * Renal insufficiency, compensated retention (creatinine \> 2.0 mg/dL) * Severe retinal Haemorrhage * Massive Haemorrhage * Known existing malignant diseases * Vasoactive concomitant medication (e.g. Naftidrofuryl, Pentoxifylline, Buflomedil, Cilostazol), or other Prostaglandins * Untreated or uncontrolled Hypertension (systolic blood pressure ≥ 180 mmHg, diastolic blood pressure ≥ 110 mmHg) * Previous participation of the patient in the present trial * Participation of the patient in a trial with the same objectives within the past 6 months, or is currently participating in another trial * Illness of the patient due to alcohol or drug-abuse within the past 6 months * Serious illness of the patient that the investigator considers to compromise his/her participation in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline | From Baseline to the end of 4 weeks of Interval Treatment (Period 2) | The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 2 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings at Baseline | From Baseline to the end of 6-months Follow-up (Period 3) | The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Pain-free Walking Distance After Period 1 in Comparison With the Findings at Baseline | From Baseline to the end of 4 weeks of Daily Treatment (Period 1) | The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 1 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Maximum Walking Distance After Period 1 in Comparison With the Findings at Baseline | From Baseline to the end of 4 weeks of Daily Treatment (Period 1) | The ratio of maximum walking distance was calculated by the maximum walking distance after Period 1 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings at Baseline | From Baseline to the end of 4 weeks of Interval Treatment (Period 2) | The ratio of maximum walking distance was calculated by the maximum walking distance after Period 2 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings After Period 1 | From the end of 4 weeks of Daily Treatment (Period 1) to the end of 4 weeks of Interval Treatment (Period 2) | The ratio of maximum walking distance was calculated by the maximum walking distance after Period 2 divided by the maximum walking distance after Period 1 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings at Baseline | From Baseline to the end of 6-months Follow-up (Period 3) | The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 1 | From the end of 4 weeks of Daily Treatment (Period 1) to the end of 4 weeks of Interval Treatment (Period 2) | The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 2 divided by the pain-free walking distance after Period 1 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 2 | From the end of 4 weeks of Interval Treatment (Period 2) to the end of 6-months Follow-up (Period 3) | The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance after Period 2 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | From Baseline to the end of 4 weeks of Daily Treatment (Period 1) | Scores for subscales were calculated by summing non-missing item scores ranging from 1 (not at all; best possible outcome) to 4 (extremely; worst possible outcome) divided by the number of non-missing items. Hence each subscale score ranges from 1 (best possible outcome) to 4 (worst possible outcome). For subscales 'Mood' and 'Treatment expectation' five items each had to be reversed in order. Additionally, subjects were asked to assess their general health and quality of life on an ordinal scale between 0 (very good) and 10 (very poor). Negative changes show a decrease from Baseline. |
| Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | From Baseline to the end of 6-months Follow-up (Period 3) | Scores for subscales were calculated by summing non-missing item scores ranging from 1 (not at all; best possible outcome) to 4 (extremely; worst possible outcome) divided by the number of non-missing items. Hence each subscale score ranges from 1 (best possible outcome) to 4 (worst possible outcome). For subscales 'Mood' and 'Treatment expectation' five items each had to be reversed in order. Additionally, subjects were asked to assess their general health and quality of life on an ordinal scale between 0 (very good) and 10 (very poor). Negative changes show a decrease from Baseline. |
| Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 1 | From the end of 4 weeks of Daily Treatment (Period 1) to the end of 6-months Follow-up (Period 3) | The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance after Period 1 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 1 | From the end of 4 weeks of Daily Treatment (Period 1) to the end of 6-months Follow-up (Period 3) | The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance after Period 1 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
| Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 2 | From the end of 4 weeks of Interval Treatment (Period 2) to the end of 6-months Follow-up (Period 3) | The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance after Period 2 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved. |
Countries
Germany
Participant flow
Recruitment details
Of the 607 screened subjects, 561 have been randomized. Of these 561 randomized subjects, 541 are included in the Full Analysis Set (FAS). FAS includes all randomized subjects who received at least one dose of trial medication and who have at least one valid measurement of pain-free walking distance under therapy.
Pre-assignment details
Participant Flow shows all randomized subjects. Baseline Characteristics refer to the FAS.
Participants by arm
| Arm | Count |
|---|---|
| Alprostadil 4-week Daily Treatment Period 1: 4 weeks of 1 x daily intravenous infusion of 3 ampoules (20 μg) of Prostaglandin E1 (total 60 μg) in 50 - 250 ml physiological saline solution over 2 hours and in addition 2 x daily (including weekends) Placebo tablets.
4-week Interval Treatment Period 2: 4 weeks of 2 x weekly intravenous infusion of 3 ampoules (20 μg) of Prostaglandin E1 (total 60 μg) in 50 - 250 ml physiological saline solution over 2 hours and in addition 2 x daily (including weekends) Placebo tablets. | 269 |
| Pentoxifylline 4-week Daily Treatment Period 1: 4 weeks of 1 x daily intravenous infusion of Placebo in 50 - 250 ml physiological saline solution over 2 hours and in addition 2 x daily (including weekends) 600 mg Pentoxifylline tablets.
4-week Interval Treatment Period 2: 4 weeks of 2 x weekly intravenous infusion of Placebo in 50 - 250 ml physiological saline solution over 2 hours and in addition 2 x daily (including weekends) 600 mg Pentoxifylline tablets. | 272 |
| Total | 541 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 22 |
| Overall Study | AE/ Unsatisfactory Compliance | 2 | 2 |
| Overall Study | AE/ Withdrawal | 1 | 4 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lack of Efficacy/ Adverse Event (AE) | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Other | 4 | 4 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Unsatisfactory Compliance of Subject | 8 | 5 |
| Overall Study | Unsatisfactory Compliance/ Withdrawal | 1 | 1 |
| Overall Study | Unsatisfactory Compl./ Lost to Follow up | 1 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 8 |
| Overall Study | Withdrawal/ Not specified | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Pentoxifylline | Alprostadil |
|---|---|---|---|
| Age categories >18 - <65 | 208 participants | 100 participants | 108 participants |
| Age categories >=65 - <75 | 233 participants | 119 participants | 114 participants |
| Age categories >=75 | 100 participants | 53 participants | 47 participants |
| Age, Continuous | 66.5 years STANDARD_DEVIATION 8.7 | 66.8 years STANDARD_DEVIATION 8.8 | 66.3 years STANDARD_DEVIATION 8.6 |
| Body Mass Index (BMI) | 26.94 kilogram/ meter^2 (kg/m^2) STANDARD_DEVIATION 3.81 | 27.11 kilogram/ meter^2 (kg/m^2) STANDARD_DEVIATION 3.75 | 26.77 kilogram/ meter^2 (kg/m^2) STANDARD_DEVIATION 3.87 |
| Duration of Primary Disease | 4.6 years STANDARD_DEVIATION 4.8 | 4.3 years STANDARD_DEVIATION 4.4 | 4.9 years STANDARD_DEVIATION 5.1 |
| Ethnicity Asian | 1 participants | 1 participants | 0 participants |
| Ethnicity Caucasian | 540 participants | 271 participants | 269 participants |
| Height | 169.7 centimeter (cm) STANDARD_DEVIATION 8.6 | 169.3 centimeter (cm) STANDARD_DEVIATION 8.6 | 170.2 centimeter (cm) STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 173 Participants | 89 Participants | 84 Participants |
| Sex: Female, Male Male | 368 Participants | 183 Participants | 185 Participants |
| Weight | 77.9 kilogram (kg) STANDARD_DEVIATION 13.7 | 77.9 kilogram (kg) STANDARD_DEVIATION 13.5 | 77.8 kilogram (kg) STANDARD_DEVIATION 13.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 60 / 276 | 55 / 285 |
| serious Total, serious adverse events | 19 / 276 | 17 / 285 |
Outcome results
Primary
Ratio of Pain-free Walking Distance After Period 1 in Comparison With the Findings at Baseline
The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 1 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From Baseline to the end of 4 weeks of Daily Treatment (Period 1)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Pain-free Walking Distance After Period 1 in Comparison With the Findings at Baseline | 1.58 meter/meter | Standard Deviation 1.92 |
| Pentoxifylline | Ratio of Pain-free Walking Distance After Period 1 in Comparison With the Findings at Baseline | 1.58 meter/meter | Standard Deviation 2.59 |
Primary
Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline
The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 2 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From Baseline to the end of 4 weeks of Interval Treatment (Period 2)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline | 2.60 meter/meter | Standard Deviation 12.22 |
| Pentoxifylline | Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline | 1.98 meter/meter | Standard Deviation 3.61 |
Primary
Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings at Baseline
The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From Baseline to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings at Baseline | 2.27 meter/meter | Standard Deviation 3 |
| Pentoxifylline | Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings at Baseline | 2.36 meter/meter | Standard Deviation 2.69 |
Secondary
Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1
Scores for subscales were calculated by summing non-missing item scores ranging from 1 (not at all; best possible outcome) to 4 (extremely; worst possible outcome) divided by the number of non-missing items. Hence each subscale score ranges from 1 (best possible outcome) to 4 (worst possible outcome). For subscales 'Mood' and 'Treatment expectation' five items each had to be reversed in order. Additionally, subjects were asked to assess their general health and quality of life on an ordinal scale between 0 (very good) and 10 (very poor). Negative changes show a decrease from Baseline.
Time frame: From Baseline to the end of 4 weeks of Daily Treatment (Period 1)
Population: Full Analysis Set (FAS). For each subscale of the questionnaire, Mean and SD are presented for non-missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Pain | -0.24 units on a scale | Standard Deviation 0.44 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Functional status | -0.21 units on a scale | Standard Deviation 0.4 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Anxiety | -0.16 units on a scale | Standard Deviation 0.51 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Mood | -0.07 units on a scale | Standard Deviation 0.34 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Social life | -0.05 units on a scale | Standard Deviation 0.34 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Expectation of treatment | -0.00 units on a scale | Standard Deviation 0.42 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | State of general health during the last week | -0.51 units on a scale | Standard Deviation 1.48 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Quality of life during the last week | -0.37 units on a scale | Standard Deviation 1.58 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Quality of life during the last week | -0.38 units on a scale | Standard Deviation 1.78 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Pain | -0.27 units on a scale | Standard Deviation 0.49 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Social life | -0.02 units on a scale | Standard Deviation 0.33 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Functional status | -0.18 units on a scale | Standard Deviation 0.41 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | State of general health during the last week | -0.36 units on a scale | Standard Deviation 1.6 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Anxiety | -0.18 units on a scale | Standard Deviation 0.54 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Expectation of treatment | 0.01 units on a scale | Standard Deviation 0.42 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 | Mood | -0.08 units on a scale | Standard Deviation 0.37 |
Secondary
Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3
Scores for subscales were calculated by summing non-missing item scores ranging from 1 (not at all; best possible outcome) to 4 (extremely; worst possible outcome) divided by the number of non-missing items. Hence each subscale score ranges from 1 (best possible outcome) to 4 (worst possible outcome). For subscales 'Mood' and 'Treatment expectation' five items each had to be reversed in order. Additionally, subjects were asked to assess their general health and quality of life on an ordinal scale between 0 (very good) and 10 (very poor). Negative changes show a decrease from Baseline.
Time frame: From Baseline to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS). For each subscale of the questionnaire, Mean and SD are presented for non-missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Pain | -0.28 units on a scale | Standard Deviation 0.57 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Functional status | -0.26 units on a scale | Standard Deviation 0.58 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Mood | -0.06 units on a scale | Standard Deviation 0.48 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Social life | -0.09 units on a scale | Standard Deviation 0.43 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Expectation of treatment | 0.07 units on a scale | Standard Deviation 0.51 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Anxiety | -0.20 units on a scale | Standard Deviation 0.64 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | State of general health during the last week | -0.43 units on a scale | Standard Deviation 1.83 |
| Alprostadil | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Quality of life during the last week | -0.36 units on a scale | Standard Deviation 2.09 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Quality of life during the last week | -0.39 units on a scale | Standard Deviation 2.2 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Pain | -0.41 units on a scale | Standard Deviation 0.58 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Expectation of treatment | 0.11 units on a scale | Standard Deviation 0.49 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Anxiety | -0.22 units on a scale | Standard Deviation 0.66 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Functional status | -0.35 units on a scale | Standard Deviation 0.57 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Mood | -0.12 units on a scale | Standard Deviation 0.53 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | State of general health during the last week | -0.48 units on a scale | Standard Deviation 1.98 |
| Pentoxifylline | Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 | Social life | -0.04 units on a scale | Standard Deviation 0.45 |
Secondary
Ratio of Maximum Walking Distance After Period 1 in Comparison With the Findings at Baseline
The ratio of maximum walking distance was calculated by the maximum walking distance after Period 1 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From Baseline to the end of 4 weeks of Daily Treatment (Period 1)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Maximum Walking Distance After Period 1 in Comparison With the Findings at Baseline | 1.39 meter/meter | Standard Deviation 0.53 |
| Pentoxifylline | Ratio of Maximum Walking Distance After Period 1 in Comparison With the Findings at Baseline | 1.43 meter/meter | Standard Deviation 1.34 |
Secondary
Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings After Period 1
The ratio of maximum walking distance was calculated by the maximum walking distance after Period 2 divided by the maximum walking distance after Period 1 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 4 weeks of Interval Treatment (Period 2)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings After Period 1 | 1.20 meter/meter | Standard Deviation 0.5 |
| Pentoxifylline | Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings After Period 1 | 1.21 meter/meter | Standard Deviation 0.41 |
Secondary
Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings at Baseline
The ratio of maximum walking distance was calculated by the maximum walking distance after Period 2 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From Baseline to the end of 4 weeks of Interval Treatment (Period 2)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings at Baseline | 1.64 meter/meter | Standard Deviation 0.86 |
| Pentoxifylline | Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings at Baseline | 1.76 meter/meter | Standard Deviation 1.78 |
Secondary
Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 1
The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance after Period 1 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 1 | 1.39 meter/meter | Standard Deviation 0.87 |
| Pentoxifylline | Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 1 | 1.42 meter/meter | Standard Deviation 0.8 |
Secondary
Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 2
The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance after Period 2 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From the end of 4 weeks of Interval Treatment (Period 2) to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 2 | 1.18 meter/meter | Standard Deviation 0.58 |
| Pentoxifylline | Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 2 | 1.17 meter/meter | Standard Deviation 0.5 |
Secondary
Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings at Baseline
The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From Baseline to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings at Baseline | 1.89 meter/meter | Standard Deviation 1.4 |
| Pentoxifylline | Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings at Baseline | 1.99 meter/meter | Standard Deviation 1.61 |
Secondary
Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 1
The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 2 divided by the pain-free walking distance after Period 1 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 4 weeks of Interval Treatment (Period 2)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 1 | 1.25 meter/meter | Standard Deviation 0.64 |
| Pentoxifylline | Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 1 | 1.24 meter/meter | Standard Deviation 0.5 |
Secondary
Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 1
The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance after Period 1 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 1 | 1.54 meter/meter | Standard Deviation 1.53 |
| Pentoxifylline | Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 1 | 1.57 meter/meter | Standard Deviation 1.1 |
Secondary
Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 2
The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance after Period 2 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
Time frame: From the end of 4 weeks of Interval Treatment (Period 2) to the end of 6-months Follow-up (Period 3)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 2 | 1.26 meter/meter | Standard Deviation 0.85 |
| Pentoxifylline | Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 2 | 1.28 meter/meter | Standard Deviation 0.74 |