Change In 6-minute Walk Distance Research Articles

Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension.

Sildenafil, approved for pulmonary arterial hypertension (PAH), has a recommended adult dose of 20 mg TID, with a previously approved 5-mg TID dose by the US Food and Drug Administration. Safety concerns arose because of common off-label use of higher doses, particularly after pediatric data linked higher doses to increased mortality. To assess this, the Food and Drug Administration mandated a study evaluating the effects of various sildenafil doses on mortality in adults with PAH. This randomized, double-blind study compared sildenafil at doses of 5, 20, or 80 mg TID in adults with PAH. The primary objective was noninferiority of 80 mg of sildenafil versus 5 mg for all-cause mortality. Secondary end points included time to clinical worsening and change in 6-minute walk distance at 6 months. Interim analyses were planned at 50% and 75% of the anticipated mortality events. Safety and tolerability were assessed in the intention-to-treat population. The study was halted after the first interim analysis, demonstrating noninferiority for 80 mg of sildenafil versus 5 mg. Of 385 patients enrolled across all dose groups, 78 died. The primary analysis showed a hazard ratio of 0.51 (99.7% CI, 0.22-1.21; P<0.001 for noninferiority) for overall survival comparing 80 mg of sildenafil with 5 mg. Time to clinical worsening favored 80 mg of sildenafil compared with 5 mg (hazard ratio, 0.44 [99.7% CI, 0.22-0.89]; P<0.001). Sildenafil at 80 mg improved 6-minute walk distance from baseline at 6 months compared with 5 mg (least square mean change, 18.9 m [95% CI, 2.99-34.86]; P=0.0201). No significant differences were found between 80 mg of sildenafil and 20 mg in mortality, clinical worsening, and 6-minute walk distance. Adverse event-related drug discontinuations were numerically higher with 80 mg of sildenafil. Sildenafil at 80 mg was noninferior to sildenafil at 5 mg when examining all-cause mortality in adults with PAH. Secondary efficacy end points favored 80 mg of sildenafil over 5 mg. On the basis of these findings, the Food and Drug Administration recently revoked the approval of 5 mg of sildenafil for adults with PAH, reinforced 20 mg TID as the recommended dose, and now allows dose titration up to 80 mg TID, if needed. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060487.

Effect of outpatient cardiac rehabilitation on motor function and health-related quality of life in stroke survivors

BackgroundOutpatient cardiac rehabilitation (CR) is a promising tool for improving functional outcome in stroke survivors, however, evidence for improving emotional health is limited. We aimed to clarify the effects of outpatient CR following in-hospital stroke rehabilitation on health-related quality of life (HRQOL) and motor function. MethodsPatients with acute ischemic stroke or transient ischemic attack discharged directly home were recruited, and 128 patients who fulfilled criteria for insurance coverage of CR were divided into the CR (+) group (n = 46) and CR (-) group (n = 82). All patients underwent in-hospital stroke rehabilitation, and within 2 months after stroke onset, patients in the CR (+) group started a 3-month outpatient CR program of supervised sessions. Changes of motor function and HRQOL assessed by the short form-36 version 2 (SF-36) from discharge to 3 months post-discharge were compared between the two groups. ResultsTwenty-six patients in the CR (+) group completed the program and 66 patients in the CR (-) group were followed up at a 3-month examination. Least-square mean changes in 6-minute walk distance and isometric knee extension muscle strength were significantly higher in the CR (+) group than the CR (-) group (52.6 vs. 16.3 m; 10.1 vs. 3.50 kgf/kg). Improvement of HRQOL at 3 months was not observed in the CR (+) group. ConclusionsOutpatient CR following in-hospital stroke rehabilitation within 2 months after stroke onset improved exercise tolerance and functional strength but not HRQOL assessed by the SF-36 after completion of CR in the present cohort.

Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study

BackgroundInhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD...

Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial.

Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04788511.

Impact of Left Heart Disease Risk Factors on Outcomes in Pulmonary Arterial Hypertension Therapy

BackgroundCurrent guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with ‘cardiopulmonary comorbidities’, despite limited available evidence to guide management. Research QuestionDo left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of PAH patients? Study Design and MethodsThe AMBITION trial criteria was used to define the phenotype of PAH patients with risk factors for LHD. Treatment strategy, functional outcome, long term survival and risk discrimination were compared with a reference PAH cohort using the PHSANZ registry. Results487 incident PAH patients diagnosed between 2011-2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors with 384 (78.9%) remaining as reference group. PAH with LHD risk factors were older (66±13 vs. 58±19years, p<0.001), had lower pulmonary vascular resistance (393±266 vs 708±391dynes/sec/cm-5, p=0.031) and worse 6-minute walk distance (286±130 vs. 327±136m, p=0.005) at diagnosis. PAH with LHD risk factors were less likely to receive less initial combination therapy (27% vs. 44%, p=0.02). Changes in 6-minute walk distance at 12-months were similar in both groups, 43±77 in PAH with LHD risk factors and 50±90m in reference group (p=0.5), including when stratified by initial treatment strategy (monotherapy: 40±81 vs. 38±95m p=0.87 and combination therapy: 53±78 vs. 64±106m, p=0.511; PAH with LHD risk factors vs. reference PAH). Functional class improvements were also similar in both groups. REVEAL 2.0 risk score effectively discriminated risk in both populations (C-statistic=0.756 for PAH with LHD risk factors and C-statistic=0.750 for reference PAH). There was no difference in survival between the two groups (log-rank test p=0.29). InterpretationIn a real-word cohort, PAH patients with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected PAH patients with LHD risk factors who were treated with initial combination therapy derived similar functional response compared to reference group. Further studies are needed to phenotype PAH patients with cardiopulmonary comorbidities who may benefit from initial combination therapy.

Group Versus Individual Rehabilitation in Lung Transplantation: A Retrospective Noninferiority Assessment

Purpose: Pulmonary rehabilitation both before and after lung transplant is associated with improved functional exercise capacity and physical quality of life. There is wide variation in rehabilitation program provision. This study's aim was to compare the effects of group versus individual rehabilitation. Methods: Individuals who completed pre- and/or posttransplant outpatient rehabilitation at a single, academic, medical center between March 2019 and March 2021 were included in this study. Noninferiority analysis was used to assess differences in change in 6-minute walk distance (6MWD) between group and individual rehabilitation. Multivariable linear regression models examined 6MWD, Short Physical Performance Battery (SPPB), Ferrans and Powers Quality of Life Index Pulmonary Version (QLI), Center for Epidemiological Studies-Depression Scale (CESD), and San Diego Shortness of Breath Questionnaire (SOBQ). Results: Preoperatively, 93 patients completed group and 81 completed individual rehabilitation. Postoperatively, 110 completed group and 105 completed individual rehabilitation. Individual rehabilitation was noninferior to group rehabilitation (α = 0.05). In addition, there was no significant difference in changes in 6MWD, SPPB, QLI, CESD, or SOBQ, between cohorts pre- and postoperatively (all P &gt; .25). Conclusions: Individual rehabilitation seems to be an acceptable alternative to group rehabilitation for lung transplant candidates and recipients.

Study Design, Rationale, and Methodology for Promote Weight Loss in Patients With Peripheral Artery Disease Who Also Have Obesity: The PROVE Trial.

Background Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6-minute walk distance at 12-month follow-up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m2 will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12-month change in 6-minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12-month follow-up and 12-month change in accelerometer-measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient-Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12-month changes in perceived exertional effort at the end of the 6-minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. Conclusions The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978.

Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial

In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and exercise function and reduced body weight in patients with obesity phenotype of heart failure and preserved ejection fraction (HFpEF). This prespecified analysis examined the effects of semaglutide on dual primary endpoints (change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body weight) and confirmatory secondary endpoints (change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP)) across obesity classes I–III (body mass index (BMI) 30.0–34.9 kg m−2, 35.0–39.9 kg m−2 and ≥40 kg m−2) and according to body weight reduction with semaglutide after 52 weeks. Semaglutide consistently improved all outcomes across obesity categories (P value for treatment effects × BMI interactions = not significant for all). In semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater with larger body weight reduction (for example, 6.4-point (95% confidence interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS and 6MWD for each 10% body weight reduction). In participants with obesity phenotype of HFpEF, semaglutide improved symptoms, physical limitations and exercise function and reduced inflammation and body weight across obesity categories. In semaglutide-treated patients, the magnitude of benefit was directly related to the extent of weight loss. Collectively, these data support semaglutide-mediated weight loss as a key treatment strategy in patients with obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511.

The Association Between Mobile App Use and Change in Functional Capacity Among Cardiac Rehabilitation Participants: Cohort Study

Cardiac rehabilitation (CR) is underused in the United States and globally, with participation disparities across gender, socioeconomic status, race, and ethnicities. The pandemic led to greater adoption of telehealth CR and mobile app use. Our primary objective was to estimate the association between CR mobile app use and change in functional capacity from enrollment to completion in patients participating in a CR program that offered in-person, hybrid, and telehealth CR. Our secondary objectives were to study the association between mobile app use and changes in blood pressure (BP) or program completion. We conducted a retrospective cohort study of participants enrolled in CR at an urban CR program in the United States. Participants were English speaking, at least 18 years of age, participated in the program between May 22, 2020, and May 21, 2022, and downloaded the CR mobile app. Mobile app use was quantified by number of exercise logs, vitals logs, and education material views. The primary outcome was change in functional capacity, measured by change in 6-minute walk distance (6MWD) from enrollment to completion. The secondary outcome was change in BP from enrollment to completion. We estimated associations using multivariable linear or logistic regression models adjusted for age, sex, race, ethnicity, socioeconomic status by ZIP code, insurance, and primary diagnosis for CR referral. A total of 107 participants (mean age 62.9, SD 13.02 years; 90/107, 84.1% male; and 57/105, 53.3% self-declared as White Caucasian) used the mobile app and completed the CR program. Participants had a mean 64.0 (SD 54.1) meter increase in 6MWD between enrollment and completion (P<.001). From enrollment to completion, participants with an elevated BP at baseline (≥130/80 mmHg) experienced a significant decrease in BP (systolic BP -11.5 mmHg; P=.002 and diastolic BP -7.7 mmHg; P=.003). We found no significant association between total app interactions and change in 6MWD (coefficient -0.03, 95% CI -0.1 to 0.07; P=.59) or change in BP (systolic coefficient 0.002, 95% CI -0.03 to 0.03; P=.87 and diastolic coefficient -0.005, 95% CI -0.03 to 0.02; P=.65). There was no significant association between total exercise logs and change in 6MWD (coefficient 0.1, 95% CI -0.3 to 0.4; P=.57) or total BP logs and change in BP (systolic coefficient -0.02, 95% CI -0.1 to 0.06; P=.63 and diastolic coefficient -0.02, 95% CI -0.09 to 0.04; P=.50). There was no significant association between total app interactions and completion of CR (adjusted odds ratio 1.00, 95% CI 0.99-1.01; P=.44). CR mobile app use as part of an in-person, hybrid, or telehealth CR program was not associated with greater improvement in functional capacity or BP or with program completion.

Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: A prospective cohort study.

Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome. In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event. 4MGS declined over 6 months (mean [95% CI] change: -0.05 [-0.09 to -0.01] m/s; p= 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan-Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >-0.07 m/s versus minor decline/improvers: ≤-0.07 m/s; p= 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23-15.83]). Similar results were observed in multiple imputation analysis. In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death.

Pulmonary vasodilator therapies in pulmonary arterial hypertension associated with CHD: a systematic review and network meta-analysis.

The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomesincluded pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.

Pediatric Population Pharmacokinetic Modeling and Exposure-Response Analysis of Ambrisentan in Pulmonary Arterial Hypertension and Comparison With Adult Data.

This study aimed to develop a population pharmacokinetic (PK) model of ambrisentan in pediatric patients (8 to <18 years) with pulmonary arterial hypertension (PAH) and compare pediatric ambrisentan systemic exposure with previously reported adult data. Association of ambrisentan exposure with efficacy (6-minute walking distance) and safety (adverse events) were exploratory analyses. A population PK model was developed using pediatric PK data. Steady-state systemic exposure metrics were estimated for the pediatric population and compared with previously reported data in adult patients with PAH and healthy subjects. No covariates had a significant effect on PK parameters; therefore, the final covariate model was the same as the base model. The pediatric population PK model was a 2-compartment model including the effect of body weight (allometric scaling),first-order absorption and elimination, and absorption lag time. Steady-state ambrisentan exposure was similar between the pediatric and adult population when accounting for body weight differences. Geometric mean area under the concentration-time curve at steady state in pediatric patients receiving ambrisentan low dose was 3% lower than in the adult population (and similar in both populations receiving high dose). Geometric mean maximum plasma concentration at steady state in pediatric patients receiving low and high doses was 11% and 18% higher, respectively, than in the adult population. There was no apparent association in the pediatric or adult population between ambrisentan exposure and change in 6-minute walking distance or incidence of ambrisentan-related adverse events in pediatric patients. The similar ambrisentan exposure and exposure-response profiles observed in pediatric and adult populations with PAH suggests appropriateness of body-weight-based dosing in the pediatric population with PAH.

Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial

BackgroundThe carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. Methods28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). ResultsAcetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). ConclusionsIn patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. ClinicalTrials.gov IdentifierNCT02755298

The relationship between longitudinal change in 6-minute walk distance and physical function in the elderly requiring long-term care.

The relationship between longitudinal change in 6-minute walk distance and physical function in the elderly requiring long-term care.

Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial

To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score<-2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P=.01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6months after initiation of iron therapy (overall P=.97). In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. NTR4487 [Netherlands Trial Registry].

Effect of Walking Course Length on 6MWT: An Experimental Study

Introduction: The 6-minute walk test (6MWT) is a validated tool of submaximal intensity used as an objective measure of functional exercise capacity. Changes in 6-minute walk distance (6MWD) are used to evaluate the efficacy of therapeutic interventions. American Thoracic Society (ATS) guidelines state that the walking course for the 6MWT must be 30 m. In a primary care physiotherapy setting, a 30 m straight course is often not available. Space limitations often force clinicians and researchers to conduct 6MWT on shorter courses. The purpose of this study was to determine the influence of 5, 10, 15, and 30 m course lengths on 6MWD and physiological parameters during the 6MWT. Materials and methods: A total of 80 healthy adults from 18 to 30 years performed four 6MWTs along 5, 10, 15, and 30 m course lengths in a corridor randomly, on consecutive days. The 6MWD and vital parameters on all four course lengths were recorded. Walking speed and maximal oxygen uptake (VO2 max) were calculated. Results: There was a significant difference in 6MWD, walking speed, and VO2 max over 5, 10, 15, and 30 m course lengths during 6MWT (p &lt; 0.05). There was no significant difference observed in the change in heart rate (HR) between 6MWT on 5 and 10 m course lengths and 6MWT on 15 and 30 m course lengths (p &gt; 0.05). Conclusion: The course length strongly influences the performance during the 6MWT and the results on 5, 10, 15, and 30 m courses are not interchangeable with each other. However, there was a similar submaximal cardiac performance on 15 and 30 m course lengths.

Abstract 13540: Characteristics of Home-Based Walking Exercise Interventions Associated With Greater Improvement in Walking Performance in Peripheral Artery Disease: A Post-Hoc Analysis of the HONOR Randomized Clinical Trial Results

Introduction: Benefits of home-based exercise (HBE) interventions in lower extremity peripheral artery disease (PAD) are variable. This post-hoc analysis of the HONOR randomized trial studied characteristics of a home-based exercise intervention associated with greater 6-minute walk improvement in PAD. Methods: HONOR was a multi-centered randomized trial. PAD participants were randomized to either a HBE intervention or usual care for 9 months. The intervention consisted of four weekly in-person visits with an exercise coach followed by 16 telephone coaching calls over the next eight months. Participants were asked to walk for exercise five days/week, wear a Fitbit to monitor activity, upload their Fitbit on the study website, and visit the website at least weekly to view their exercise goals and monitor their progress toward exercise goals. The primary outcome was change in 6-minute walk distance at 9-month follow-up. Results: Of 200 people randomized (age 70 yrs. ±10.4, 52.5% female, 50% Black), 182 (91%) completed nine-month follow-up. Overall, the exercise intervention did not improve 6-minute walk compared to usual care [+5.5 vs. +14.4 m respectively (Mean diff: –8.9 m, 95% CI, –26.0, +8.2 m, P = .31)]. Among the 99 people randomized to HBE, change in 6-minute walk ranged from -239.2-233.7. See table for characteristics associated with greater six-minute walk improvement. Conclusion: In a home-based exercise intervention for PAD, more frequent use of the intervention website and greater exercise sessions/week, but not more time wearing a Fitbit, were associated with greater 6-minute walk improvement. Future home-based exercise interventions for PAD should help patients self-monitor exercise behavior and increase exercise sessions per week.

Abstract 11480: Telmisartan to Improve Walking Performance in People With Lower Extremity Peripheral Artery Disease: The Telex Randomized Clinical Trial

BACKGROUND. People with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan, an angiotensin receptor blocker (ARB), has properties that reverse these abnormalities. This randomized clinical trial tested whether telmisartan improved six-minute walk distance, compared to placebo, in people with PAD at 6-month follow-up. METHODS. This multi-centered randomized clinical trial was designed as a 2 x 2 factorial design, comparing the effects of telmisartan plus supervised exercise therapy (SET) to telmisartan alone and SET alone, respectively and comparing telmisartan alone to placebo. PAD participants were randomized to one of four groups: telmisartan+SET (N=30), telmisartan + attention control (N=29), placebo + SET (N=28), or placebo+ attention control (N=27) for six months. Due to slower than anticipated enrollment, the primary comparison was changed to a comparison of the two telmisartan groups combined to the two placebo groups combined. The primary outcome was 6-month change in 6-minute walk distance. Secondary outcomes were maximal treadmill walking distance, the Walking Impairment Questionnaire distance, speed, and stair climbing scores, and the short-form 36 physical functioning score. Results adjusted for site, baseline six-minute walk distance, randomization to SET vs. attention control, and group differences in the prevalence of sex and heart failure at baseline. RESULTS. Of 114 randomized patients (mean [SD] age, 67.3 [9.9] years, 46 (40.4%) female, 81 (71.1%) Black), 105 (92%) completed 6-month follow-up. See the Table for results. CONCLUSIONS. These results do not support telmisartan for improving objectively measured walking performance or patient reported outcomes in patients with PAD.

Effect of Telmisartan on Walking Performance in Patients With Lower Extremity Peripheral Artery Disease

Patients with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan (an angiotensin receptor blocker) has properties that reverse these abnormalities. To determine whether telmisartan improves 6-minute walk distance, compared with placebo, in patients with lower extremity PAD at 6-month follow-up. Double-blind, randomized clinical trial conducted at 2 US sites and involving 114 participants. Enrollment occurred between December 28, 2015, and November 9, 2021. Final follow-up occurred on May 6, 2022. The trial randomized patients using a 2 × 2 factorial design to compare the effects of telmisartan plus supervised exercise vs telmisartan alone and supervised exercise alone and to compare telmisartan alone vs placebo. Participants with PAD were randomized to 1 of 4 groups: telmisartan plus exercise (n = 30), telmisartan plus attention control (n = 29), placebo plus exercise (n = 28), or placebo plus attention control (n = 27) for 6 months. The originally planned sample size was 240 participants. Due to slower than anticipated enrollment, the primary comparison was changed to the 2 combined telmisartan groups vs the 2 combined placebo groups and the target sample size was changed to 112 participants. The primary outcome was the 6-month change in 6-minute walk distance (minimum clinically important difference, 8-20 m). The secondary outcomes were maximal treadmill walking distance; Walking Impairment Questionnaire scores for distance, speed, and stair climbing; and the 36-Item Short-Form Health Survey physical functioning score. The results were adjusted for study site, baseline 6-minute walk distance, randomization to exercise vs attention control, sex, and history of heart failure at baseline. Of the 114 randomized patients (mean age, 67.3 [SD, 9.9] years; 46 were women [40.4%]; and 81 were Black individuals [71.1%]), 105 (92%) completed 6-month follow-up. At 6-month follow-up, telmisartan did not significantly improve 6-minute walk distance (from a mean of 341.6 m to 343.0 m; within-group change: 1.32 m) compared with placebo (from a mean of 352.3 m to 364.8 m; within-group change: 12.5 m) and the adjusted between-group difference was -16.8 m (95% CI, -35.9 m to 2.2 m; P = .08). Compared with placebo, telmisartan did not significantly improve any of the 5 secondary outcomes. The most common serious adverse event was hospitalization for PAD (ie, lower extremity revascularization, amputation, or gangrene). Three participants (5.1%) in the telmisartan group and 2 participants (3.6%) in the placebo group were hospitalized for PAD. Among patients with PAD, telmisartan did not improve 6-minute walk distance at 6-month follow-up compared with placebo. These results do not support telmisartan for improving walking performance in patients with PAD. ClinicalTrials.gov Identifier: NCT02593110.

Efficacy and dose-response relationship of oral treprostinil in PAH patients on monotherapy or dual background therapy

Abstract Background FREEDOM-C and FREEDOM-C2 were randomized, placebo-controlled, double-blinded international, multicenter studies investigating the use of oral treprostinil (TRE) in subjects on mono or dual background pulmonary arterial hypertension (PAH) therapies. Both had a primary endpoint of change in 6-minute walk distance (6MWD) at Week 16 vs baseline. Previous post-hoc analyses combining mono and dual therapy subjects (PDE-5i and/or ERA) from these studies revealed a TRE dose-dependent increase in 6MWD. (1. White &amp; Rao, 2016) Purpose This post-hoc analysis was performed to determine if subjects from FREEDOM-C and FREEDOM-C2 derive improvements in 6MWD with increasing doses of TRE when stratified by mono or dual background therapy and to determine if PAH background therapies (mono or dual) impacted 6MWD. Methods All active subjects (n=331) from FREEDOM-C and FREEDOM-C2 were grouped into TRE dose tertiles (low-dose: ≤2 mg BID, mid-dose: &amp;gt;2 mg to ≤3.5 mg BID, and high-dose: &amp;gt;3.5 mg BID). Placebo subjects (n=329) were in a separate 0 mg dose group. No data imputation was implemented. Comparisons of 6MWD change at Weeks 4, 8, 12, and 16 between mono and dual therapy subgroups at any dose group were performed using a two-sample t-test or nonparametric Wilcoxon rank-sum test. The nonparametric Kruskal-Wallis test was conducted with subsequent pairwise comparisons of 6MWD change at Week 16 between the four dose groups through Dunn's approach. Additionally, the Jonckheere-Terpstra test was used to assess the linear trend for 6MWD improvement with higher doses of TRE. Results Baseline characteristics of the combined intention to treat (ITT) population and summary of 6MWD for subjects with both baseline and Week 16 data are in Table 1. 6MWD change improved steadily to Week 16 in subjects at higher TRE doses, regardless of the number of PAH background therapies (Figure 1). No statistical differences were found between mono and dual therapy at any time point or for any dose group. At Week 16, there was a significant difference in 6MWD change between the placebo group and high dose group within both mono and dual background therapy subjects. The difference between the low- and high-dose groups was significant for subjects on dual background therapy. There was a significant positive linear trend for TRE doses in 6MWD improvement at Week 16 for both monotherapy subjects (one-sided p-value = 0.0002) and dual therapy subjects (one-sided p-value = 0.0242). Conclusions 6MWD improved in PAH patients regardless of their background therapy (monotherapy or dual background) and derive greater 6MWD improvements with higher doses of TRE. The observed dose-dependent 6MWD increase supports the use of TRE in sequential combination with background therapies (mono or dual). Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): United Therapeutics Corporation