Clinical trial NCT05467735: Above-Knee-High Application of Lower Limb Compression and Its Impact on Clinical Outcome in Patients Hospitalized With Heart Failure Exacerbation.
Official title: Above-Knee-High Application of Lower Limb Compression and Its Impact on Clinical Outcome in Patients Hospitalized With Heart Failure Exacerbation.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Heart Failure; With Decompensation
Lower Extremity Edema
Heart Failure，Congestive
Keywords: Heart failure with decompensation
Compression stockings
Lower extremity compression
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2022-07-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Heart failure (HF) remains one of the most common causes of hospitalization with high morbidity and mortality, and its worldwide prevalence is increasing. Despite notable progress in outcomes for HF the rate of early rehospitalization for HF (re-HHF) remains high, especially in the first 30 days. The rate of 30-day HF rehospitalization in the claims databases of the USA and in worldwide randomized clinical trials is 20-25% and 5-10% respectively.

In patients with bilateral leg edema, the presence of CHF (congestive heart failure) as the factor causing or worsening local leg swelling should be evaluated. Application of local leg compression can be considered in stable CHF patients without decompensated heart function (NYHA Class I and II) for both CHF-related edema treatment and for treatment of concomitant diseases leading to leg swelling occurrence. Current literature does not have recommendations on the routine use of lower limb compression in leg swelling related to end stage heart disease and advanced, decompensated heart failure. Potential benefits of applying medical compression in more severe classes of CHF (NYHA Class III and IV) would need to be evaluated by further randomized clinical studies to determine which cohort of patients would benefit most from lower limb compression, as well as to choose the safest and most efficient compression protocol for these patients.

The AIM of this study is to improve the clinical outcome of patients admitted with exacerbation of heart failure with associated volume overload.

The primary objectives are: 1) diminish the duration of hospitalization of CHF patients; 2) decrease the incidence of rehospitalization from CHF exacerbation and 3) prevent local complications associated with prolonged lower extremity edema.

The investigators hypothesize that the application of local compression to bilateral lower extremities, when added to guideline-based therapy for CHF exacerbation, will improve overall clinical outcome in patients at the University of Texas Medical Branch (UTMB). If our intervention is proven to be beneficial, it could lead to a significant reduction in nationwide hospitalization costs associated with heart failure.

Detailed description: The growing number of patients with potentially heart-affecting diseases, including arterial hypertension, diabetes, and heart ischemic disease, as well as the ageing of the population, has resulted in a growing number of patients with advanced stages of CHF. The average number of days for an HF-related hospitalization in the United States is about 6 to 8 days. Hospitalization costs associated with heart failure averaged $23,077 and were higher when heart failure was a secondary rather than the primary diagnosis.

The presence of CHF results in a significant risk of leg oedema. Medical compression (MC) treatment is one of the basic methods of leg oedema elimination in patients with chronic venous disease and lymphedema, but it is not routinely considered in subjects with CHF-related swelling. In addition to chronic venous disease, bilateral leg swelling can also occur in other pathological conditions, including occupational leg oedema, lymphedema, obesity, or hypoalbuminemia. Lower extremity edema can significantly affect the patient's general condition and quality of life. The symptoms of leg heaviness, cramps \& mobility limitations could be accompanied by signs of local skin injuries, transcutaneous migration of fluid, skin discoloration or stasis dermatitis and skin induration. In more advanced and permanent swelling, the sequence of fluid transudation and epithelial maceration can lead to the development of large skin and subcutaneous tissue defects, with formation of chronic lower extremity ulcers. In cases where lower extremity lesions or wounds are already present, the presence of heart failure with volume overload can significantly impair the healing process of the local pathology.

Despite the common use of compression therapy in the treatment of leg swelling of venous and lymphatic origin, guidelines regarding its potential use in HF-related edema have not been specified. This is due to lack of sufficient number of properly performed studies in this field as well as a heterogenous population of heart failure patients with several classes of disease severity. As documented in the available literature, compression treatment can potentially be used in selected HF patients.

Patients who are admitted with heart failure exacerbation with clinical evidence of volume overload in the form of lower extremity edema will be randomly assigned in a 1:1 ratio to either the Control group or Compression group.

Patients, care providers (Heart failure specialist) and outcome-assessing physicians would be blinded to arm assignment.

Patients in the Compression group would be subject to application of standardized lower extremity, thigh-high, elastic compression stockings within 24 hours of admission, and would remain in place during the entire hospital stay, provided the patient is able to tolerate it.

In addition, the patients would be closely monitored with daily skin checks for cutaneous lesions and daily transthoracic echocardiograms for estimation on cardiac pressures.

Orthostatic vitals signs would be checked on Day 2 or Day 3 of hospitalization by a member of the study team.

In the Control group, the inflatable sleeves of a sequential compression device would be placed in bilateral lower extremities, but the device would not be turned on, thus no external pressure would be applied. All other measures would be identical to the Compression group.

Both groups of patients would receive standard care for heart failure exacerbation.

The primary outcomes would be-

1. Length of stay in the hospital, calculated by subtracting the day of admission from day of discharge. Incidence of rehospitalization due to heart failure exacerbation within the first 30 days as well as within the first 90 days after discharge from index hospitalization. Patients would have been recruited and subject to our intervention at the index hospitalization.
2. Duration of index hospitalization.

The secondary outcomes would be incidence of rehospitalization due to heart failure exacerbation within the first 30 days as well as within the first 90 days after discharge from index hospitalization. In addition, the following would also be secondary outcomes of our study: death from all causes, cardiovascular deaths, and major adverse cardiac event within 30 days of discharge from index hospitalization, incidence of AKI, total duration of IV diuretics therapy, percent change in serum BNP level at discharge in comparison to admission. Incidence of orthostatic hypotension and incidence of cutaneous lesions following application of compression stockings would be secondary outcomes as well.

Following IRB approval, the recruiting process will begin with a target of including 100 patients in the study. Tentative timeline for completion of the study would be three (3) years.

Patients who meet the inclusion criteria of the study will be randomly assigned in a 1:1 ratio to either the Control group or Compression group. Randomization will be performed by data analysis software, which would determine whether the patient would fall under the lower extremity Compression arm vs Control (no compression) arm.

Patients in the Compression group would be subject to application of standardized lower extremity, thigh-high, elastic compression stockings within 24 hours of admission. The stockings used at UTMB are known to exert a pressure ranging from 15-18 mmHg, with the greatest pressure being exerted at the ankle (18 mmHg) and gradual reduction throughout the length of the leg to 15 mmHg. Appropriate size of the stockings would be based on calf circumference, thigh circumference and leg length. The compression would be applied throughout the entire duration of hospitalization, provided the patient is able to tolerate it. Daily thorough skin checks for any cutaneous defects or lesions will be performed, and mobilization encouraged. Orthostatic blood pressure would be checked at least 24 hours after application of compression stockings, either on day 2 or 3 of hospitalization. In addition, bedside Transthoracic Echocardiograms would be done prior to the application of compression and on a daily basis after the stockings had been placed to monitor intra-cardiac pressures. However, the pressures obtained from echocardiogram would not be made available to the heart failure team to ensure that the ongoing treatment is not affected in any way by echocardiographic findings of the study team.

The investigators would measure thigh and calf circumference every day. If there is a change (either increase or decrease) in the circumferences by 3-5 cm from the previous day, investigators would consider changing the size of compression stocking based on the new measurements.

In the Control group, the inflatable sleeves of a sequential compression device would be placed in bilateral lower extremities, but the device would not be turned on, thus no external pressure would be applied. Orthostatic blood pressure measurements, daily skin checks and bedside echocardiograms prior to and after application of lower extremity sleeves would be performed similar to the compression group. No extra costs on the part of the patient would be necessary.

Eligibility criteria: Inclusion Criteria:

1. Patients who are admitted with heart failure exacerbation with clinical evidence of volume overload in the form of lower extremity pitting edema.
2. Patients who are not yet recruited for other pharmacological or medical device clinical trials.

Exclusion Criteria:

1. Age \<18 years.
2. Patient on hemodialysis or peritoneal dialysis.
3. Simultaneous participation in another interventional study.
4. Impossibility to perform lower extremity compression, caused by pathology in either or both lower limbs (e.g. amputation, chronic wounds).
5. No written informed consent.
6. Patient who are on invasive or non-invasive positive pressure ventilation (including BiPAP) or who are requiring \>15L of oxygen.
7. Cardiogenic shock requiring catecholamine infusion.
8. Systolic blood pressure \<80 mmHg.
9. Patients requiring mechanical circulatory support including intra-aortic balloon counter-pulsation or impella.
10. Patients on VAD (Ventricular Assist Device).
11. Severe peripheral artery disease
12. Diagnosis of lower extremity deep venous thrombosis or pulmonary embolism in the last 3 months
13. Expected impossibility to obtain follow-up data at 12-week follow-up.
14. Pregnant women.

Primary outcomes:
measure: Length of stay in the hospital
timeFrame: up to 60 days
Secondary outcomes:
measure: Incidence of 30-day rehospitalization
timeFrame: The incidence of rehospitalization or readmission within the first 30 days after discharge
measure: Incidence of 90-day rehospitalization
timeFrame: The incidence of rehospitalization or readmission within the first 90 days after discharge
measure: Death from all causes
timeFrame: Death from all causes within the first 30 days as well as within the first 90 days after discharge from index hospitalization
measure: Cardiovascular deaths
timeFrame: Cardiovascular deaths within the first 30 days as well as within the first 90 days after discharge from index hospitalization
measure: Major adverse cardiac event within 30 days of discharge from index hospitalization
timeFrame: Major adverse cardiac event within the first 30 days as well as within the first 90 days after discharge from index hospitalization
measure: Incidence of AKI
timeFrame: Up to 60 days
measure: Duration of IV diuretics therapy
timeFrame: up to 30 days
measure: Change in serum BNP level at discharge in comparison to admission
timeFrame: up to 60 days
measure: Incidence of orthostatic hypotension
timeFrame: after 48 hours but before 72 hours after application of compression stocking
measure: Incidence of cutaneous lesions following application of compression stockings.
timeFrame: up to 60 days
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch (UTMB) Galveston
state: Texas
Study officials:
affiliation: University of Texas Medical Branch, Galveston
name: Wissam I Khalife, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Medical Branch, Galveston
name: Salman Salehin, MD
role: PRINCIPAL_INVESTIGATOR
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