Peripheral Artery Disease
Conditions
Brief summary
The TELEX trial will establish whether telmisartan alone improves walking performance in people with peripheral artery disease (PAD). The TELEX trial will also determine whether telmisartan plus supervised exercise improves walking performance more than either therapy alone. TELEX is a randomized controlled clinical trial (2 x 2 factorial design) of 112 participants with PAD randomized to one of four arms: Group A: telmisartan + supervised exercise therapy; Group B: telmisartan + a no exercise control group; Group C: placebo + supervised exercise therapy; and Group D: placebo + a no exercise control group.
Interventions
BEHAVIORALSupervised Treadmill Exercise Therapy
Participants randomized to the exercise intervention will receive supervised treadmill exercise three times weekly for six months.
DRUGTelmisartan
Participants randomized to the telmisartan arm of the study will take 20 mg or 40 mg of telmisartan daily based on the results of their study run-in. Participants will have their dose increased to up to 80 mg as tolerated.
OTHERNo exercise control group
Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months.
DRUGPlacebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All participants will have PAD. PAD will be defined as follows. First, an ABI \<= 0.90 at the baseline study visit is an inclusion criterion for PAD. Second, potential participants who have an ABI \> 0.90 but ≤ 1.00 and experience a 20% or higher drop in ABI after heel-rise exercise will be eligible. Third, potential participants with an ABI \> 0.90 who have vascular lab evidence of PAD or angiographic evidence of PAD will be eligible. Finally, potential participants with a history of lower extremity revascularization who do not meet the criterion above and have an ABI \> 0.90 with a 20% or higher drop in ABI after heel-rise exercise will be eligible.
Exclusion criteria
1. Above or below knee amputation, critical limb ischemia, wheelchair confinement, inability to walk without a walker, or current foot ulcer. 2. Walking is limited by a condition other than PAD. 3. \> Class II NYHA heart failure or angina, increase in angina, angina at rest, or abnormal baseline treadmill stress test. Potential participants may become eligible following an abnormal baseline treadmill stress test if they have evidence of an absence of coronary ischemia based on testing with their own physician. 4. Currently taking an angiotensin receptor blocker or an ACE inhibitor or use of these medications in the past three months. 5. Currently taking aliskiren (Tekturna). 6. Blood pressure \< 100/50 at baseline or potassium \> 5.0 meq/L at baseline. 7. Blood pressure \< 100/50 after run-in or potassium \>= 5.5 meq/L at the end of run-in. 8. Severe hepatic impairment defined by two or more liver function enzyme values greater than 2.5 the upper limit of normal. 9. Acute decline in renal function on telmisartan, defined as a 30% or greater decline in eGFR following the two-week run-in as compared to baseline. If the participant had a baseline eGFR performed by his/her physician within two months of the baseline eGFR for the TELEX trial, the participant's physician's eGFR may be considered the baseline measure, at the study principal investigator's discretion. 10. Allergy to ARBs. 11. Failure to successfully complete the 2-week study run-in, defined as failing to attend the health education and treadmill exercise run-in sessions and/or failing to take the study medication daily for 10 or more days in the two-week period (i.e. one pill per day for \> 10 days out of the 14 day run-in period). 12. Surgery including lower extremity revascularization, coronary revascularization with stenting, or orthopedic surgery during the past 3 months or anticipated in the next 6 months or myocardial infarction or stroke in the past 3 months. 13. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.\] 14. MMSE score \< 23 or dementia. 15. Currently walking regularly for exercise at a level similar to the study intervention. 16. Participation in another clinical trial or cardiac rehabilitation or completion of a clinical trial or cardiac rehabilitation in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing an exercise intervention or a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\] 17. Non-English speaking, a visual impairment that limits walking ability, or a hearing impairment that interferes with study participation. 18. Congestive heart failure with an ejection fraction \<40. 19. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six-minute Walk Performance | Change from baseline to six-month follow-up | We will determine whether telmisartan therapy with or without exercise improves six-minute walk distance at 6-month follow-up, compared to placebo with or without exercise (i.e. two group comparisons of all participants randomized to telmisartan vs. all participants randomized to placebo). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Treadmill Walking Distance | Change from baseline to six-month follow-up | In the treadmill walking test, participants walk on either a gardner or modified gardner protocol until they stop the test. Distance walked is recorded. |
| Walking Impairment Questionnaire (WIQ) Distance Score | Change from baseline to six-month follow-up | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| SF-36 Physical Functioning Score | Change from baseline to six-month follow-up | The SF-36 physical functioning score will be used to measure quality of life. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Walking Impairment Questionnaire (WIQ) Speed Score | Change from baseline to six-month follow-up | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Walking Impairment Questionnaire (WIQ) Stair-climbing Score | Change from baseline to six-month follow-up | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy Participants in this group will receive both daily telmisartan and supervised treadmill exercise three days weekly for six months.
Supervised Treadmill Exercise Therapy: Participants randomized to the exercise intervention will receive supervised treadmill exercise three times weekly for six months.
Telmisartan: Participants randomized to the telmisartan arm of the study will take 20 mg or 40 mg of telmisartan daily based on the results of their study run-in. Participants will have their dose increased to up to 80 mg as tolerated. | 30 |
| Telmisartan + No Exercise Control Group Participants in this group will receive daily telmisartan and attend weekly educational lectures at the medical center for six months.
Telmisartan: Participants randomized to the telmisartan arm of the study will take 20 mg or 40 mg of telmisartan daily based on the results of their study run-in. Participants will have their dose increased to up to 80 mg as tolerated.
No exercise control group: Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months. | 29 |
| Placebo + Supervised Treadmill Exercise Therapy Participants randomized to this group will receive daily placebo and supervised treadmill exercise three times weekly for six months.
Supervised Treadmill Exercise Therapy: Participants randomized to the exercise intervention will receive supervised treadmill exercise three times weekly for six months.
Placebo | 28 |
| Placebo + No Exercise Control Group Participants randomized to this group will receive daily placebo and health education lectures weekly for six months.
No exercise control group: Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months.
Placebo | 27 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 3 | 2 |
Baseline characteristics
| Characteristic | Telmisartan + No Exercise Control Group | Placebo + Supervised Treadmill Exercise Therapy | Telmisartan + Supervised Treadmill Exercise Therapy | Placebo + No Exercise Control Group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 10 | 65.8 years STANDARD_DEVIATION 9.4 | 68.5 years STANDARD_DEVIATION 8.9 | 67.9 years STANDARD_DEVIATION 11.5 | 67.3 years STANDARD_DEVIATION 9.9 |
| Ankle-brachial index | 0.77 ratio STANDARD_DEVIATION 0.3 | 0.78 ratio STANDARD_DEVIATION 0.23 | 0.67 ratio STANDARD_DEVIATION 0.23 | 0.69 ratio STANDARD_DEVIATION 0.17 | 0.73 ratio STANDARD_DEVIATION 0.24 |
| Body mass index | 27.61 kg/m^2 STANDARD_DEVIATION 6.23 | 28.73 kg/m^2 STANDARD_DEVIATION 6.4 | 30.45 kg/m^2 STANDARD_DEVIATION 7.49 | 28.20 kg/m^2 STANDARD_DEVIATION 5.75 | 28.77 kg/m^2 STANDARD_DEVIATION 6.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 26 Participants | 27 Participants | 26 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 18 Participants | 22 Participants | 20 Participants | 81 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 5 Participants | 9 Participants | 6 Participants | 6 Participants | 26 Participants |
| Sex: Female, Male Female | 10 Participants | 15 Participants | 12 Participants | 9 Participants | 46 Participants |
| Sex: Female, Male Male | 19 Participants | 13 Participants | 18 Participants | 18 Participants | 68 Participants |
| Six-min walk distance | 359.62 meters STANDARD_DEVIATION 84.41 | 317.42 meters STANDARD_DEVIATION 123.31 | 327.30 meters STANDARD_DEVIATION 96.58 | 374.55 meters STANDARD_DEVIATION 122.4 | 344.29 meters STANDARD_DEVIATION 108.51 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 29 | 1 / 28 | 0 / 27 |
| other Total, other adverse events | 20 / 30 | 15 / 29 | 23 / 28 | 18 / 27 |
| serious Total, serious adverse events | 4 / 30 | 5 / 29 | 6 / 28 | 7 / 27 |
Outcome results
Primary
Six-minute Walk Performance
We will determine whether telmisartan therapy with or without exercise improves six-minute walk distance at 6-month follow-up, compared to placebo with or without exercise (i.e. two group comparisons of all participants randomized to telmisartan vs. all participants randomized to placebo).
Time frame: Change from baseline to six-month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy | Six-minute Walk Performance | 5.86 meters | Standard Deviation 67.21 |
| Telmisartan + No Exercise Control Group | Six-minute Walk Performance | -3.92 meters | Standard Deviation 47.33 |
| Placebo + Supervised Treadmill Exercise Therapy | Six-minute Walk Performance | 30.27 meters | Standard Deviation 29.44 |
| Placebo + No Exercise Control Group | Six-minute Walk Performance | -4.62 meters | Standard Deviation 42.54 |
p-value: 0.110795% CI: [-54.59, 5.78]ANCOVA
p-value: 0.537895% CI: [-21.84, 41.39]ANCOVA
p-value: 0.95695% CI: [-24.96, 26.38]ANCOVA
Secondary
Maximal Treadmill Walking Distance
In the treadmill walking test, participants walk on either a gardner or modified gardner protocol until they stop the test. Distance walked is recorded.
Time frame: Change from baseline to six-month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy | Maximal Treadmill Walking Distance | 207.99 meters | Standard Deviation 150.44 |
| Telmisartan + No Exercise Control Group | Maximal Treadmill Walking Distance | 66.21 meters | Standard Deviation 226.81 |
| Placebo + Supervised Treadmill Exercise Therapy | Maximal Treadmill Walking Distance | 176.64 meters | Standard Deviation 259.51 |
| Placebo + No Exercise Control Group | Maximal Treadmill Walking Distance | 80.96 meters | Standard Deviation 178.73 |
p-value: 0.612195% CI: [-92.42, 155.12]ANCOVA
p-value: 0.011695% CI: [33.14, 250.42]ANCOVA
p-value: 0.814695% CI: [-140.89, 111.39]ANCOVA
Secondary
SF-36 Physical Functioning Score
The SF-36 physical functioning score will be used to measure quality of life. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Change from baseline to six-month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy | SF-36 Physical Functioning Score | 0.69 score on a scale | Standard Deviation 21.16 |
| Telmisartan + No Exercise Control Group | SF-36 Physical Functioning Score | 5.96 score on a scale | Standard Deviation 20.69 |
| Placebo + Supervised Treadmill Exercise Therapy | SF-36 Physical Functioning Score | 8.75 score on a scale | Standard Deviation 21.68 |
| Placebo + No Exercise Control Group | SF-36 Physical Functioning Score | 0.21 score on a scale | Standard Deviation 20.56 |
p-value: 0.178295% CI: [-19.91, 3.79]ANCOVA
p-value: 0.355595% CI: [-16.61, 6.07]ANCOVA
p-value: 0.329495% CI: [-5.99, 17.49]ANCOVA
Secondary
Walking Impairment Questionnaire (WIQ) Distance Score
The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Change from baseline to six-month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy | Walking Impairment Questionnaire (WIQ) Distance Score | 8.77 score on a scale | Standard Deviation 26.35 |
| Telmisartan + No Exercise Control Group | Walking Impairment Questionnaire (WIQ) Distance Score | 6.33 score on a scale | Standard Deviation 33.69 |
| Placebo + Supervised Treadmill Exercise Therapy | Walking Impairment Questionnaire (WIQ) Distance Score | 7.85 score on a scale | Standard Deviation 12.42 |
| Placebo + No Exercise Control Group | Walking Impairment Questionnaire (WIQ) Distance Score | -0.55 score on a scale | Standard Deviation 17.91 |
p-value: 0.875595% CI: [-10.84, 12.68]ANCOVA
p-value: 0.765195% CI: [-13.83, 18.7]ANCOVA
p-value: 0.377695% CI: [-8.65, 22.41]ANCOVA
Secondary
Walking Impairment Questionnaire (WIQ) Speed Score
The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Change from baseline to six-month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy | Walking Impairment Questionnaire (WIQ) Speed Score | 2.74 score on a scale | Standard Deviation 25.64 |
| Telmisartan + No Exercise Control Group | Walking Impairment Questionnaire (WIQ) Speed Score | 4.81 score on a scale | Standard Deviation 26.41 |
| Placebo + Supervised Treadmill Exercise Therapy | Walking Impairment Questionnaire (WIQ) Speed Score | 11.46 score on a scale | Standard Deviation 16.52 |
| Placebo + No Exercise Control Group | Walking Impairment Questionnaire (WIQ) Speed Score | 1.72 score on a scale | Standard Deviation 17.36 |
p-value: 0.156995% CI: [-20.91, 3.47]ANCOVA
p-value: 0.769295% CI: [-16.16, 12.02]ANCOVA
p-value: 0.630695% CI: [-9.74, 15.91]ANCOVA
Secondary
Walking Impairment Questionnaire (WIQ) Stair-climbing Score
The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Change from baseline to six-month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + Supervised Treadmill Exercise Therapy | Walking Impairment Questionnaire (WIQ) Stair-climbing Score | 2.73 score on a scale | Standard Deviation 34.81 |
| Telmisartan + No Exercise Control Group | Walking Impairment Questionnaire (WIQ) Stair-climbing Score | 3.37 score on a scale | Standard Deviation 28.58 |
| Placebo + Supervised Treadmill Exercise Therapy | Walking Impairment Questionnaire (WIQ) Stair-climbing Score | 10.59 score on a scale | Standard Deviation 24.14 |
| Placebo + No Exercise Control Group | Walking Impairment Questionnaire (WIQ) Stair-climbing Score | -2.08 score on a scale | Standard Deviation 21.21 |
p-value: 0.354295% CI: [-24.74, 9.02]ANCOVA
p-value: 0.941795% CI: [-17.98, 16.71]ANCOVA
p-value: 0.450895% CI: [-8.96, 19.86]ANCOVA