Ultrasound Evaluation of the IVC in Addition to Clinical Assessment to Guide Decongestion in ADHF (CAVA-ADHF)

Ultrasound Evaluation of the Inferior Vena Cava in Addition to Clinical Assessment to Guide Decongestion in Acute Decompensated Heart Failure: a Pilot Study

CAVA-ADHF is designed as a prospective, randomized, controlled, patient-blinded, multicenter, parallel-group trial. The objective is to test whether evaluation of the inferior vena cava diameter in addition to clinical assessment is superior compared to clinical assessment alone with respect to the surrogate endpoint of change in NT-proBNP from baseline to discharge. The CAVA-ADHF trial is supported by the Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK).

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Diagnostic test: Ultrasound evaluation of the inferior vena cava diameter; Diagnostic test: Sham ultrasound evaluation of the inferior vena cava diameter

Detailed Description

Only limited evidence is available on the best method to monitor and guide decongestion in acute decompensated heart failure. Therefore, no specific guideline recommendations are made in this regard. It is unknown whether an objective congestion marker can be used to guide decongestion or such marker is only of prognostic value by identifying high-risk patients with an advanced disease state.

CAVA-ADHF is designed as prospective, randomized, controlled, patient-blinded, multicenter, parallel-group trial and aims to demonstrate effectiveness of inferior vena cava (IVC)-guided decongestion, its feasibility, and to estimate effect size and variability of clinical endpoints following the intention-to-treat principle.

After inclusion and exclusion criteria have been checked patients will be randomized:

Experimental intervention: Decongesting treatment guided by clinical assessment and ultrasound evaluation of the IVC diameter. Decongestion should lead to a maximal IVC diameter ≤2.1 cm and IVC collapsibility index >50% in addition to relief of symptoms and signs of congestion before discharge.

Control intervention: Decongesting treatment guided by clinical assessment alone. The IVC ultrasound evaluation is performed, but results are not reported to treating physicians.

Trial intervention will end with discharge from the index hospitalization. Patients will be followed-up for 180 to 210 days after randomization.

The CAVA-ADHF trial is supported by the Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK).

• Study Type: Interventional
• Enrollment (Actual): 388
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Lübeck, Germany, 23538
    • Universitäres Herzzentrum Lübeck

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalization for ADHF with dyspnea ≥NYHA III, peripheral edema, and pulmonary congestion (rales on auscultation or pulmonary vascular congestion on chest radiograph)
• Age ≥18 years
• NT-proBNP >300 ng/l within 24 h after admission
• Sufficient ultrasound visualization to evaluate IVC
• IVCmax >2.1 cm and IVCCI ≤50 % in the baseline assessment within 24 h after admission
• Capability to sign informed consent personally

Exclusion Criteria:

• Cardiogenic shock with systolic blood pressure <90 mmHg plus end-organ hypoperfusion
• ADHF due to significant arrhythmias
• Severe pulmonary disease as primary cause of dyspnea
• Simplified Modification of Diet in Renal Disease estimated glomerular filtration rate <30 ml/min/1.73 m²
• Need for non-invasive or invasive ventilation support at baseline
• Pregnancy
• Participation in another interventional trial regarding heart failure treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clinical assessment plus IVC diameter; Decongesting treatment guided by clinical assessment and ultrasound evaluation of the inferior vena cava diameter	Diagnostic test: Ultrasound evaluation of the inferior vena cava diameter; Treatment will be guided by clinical assessment and ultrasound evaluation of the inferior vena cava (IVC) diameter. Decongestion should lead to maximal IVC diameter ≤2.1 cm and IVC collapsibility index >50% in addition to relief of symptoms and signs of congestion before discharge.
Sham Comparator: Clinical assessment only; Decongesting treatment guided by clinical assessment alone	Diagnostic test: Sham ultrasound evaluation of the inferior vena cava diameter; Teatment guided by clinical assessment alone. Decongestion should lead to relief of symptoms and signs of congestion before discharge. IVC ultrasound evaluation is performed, but results are not reported to treating physicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NT-proBNP from baseline to discharge	The core laboratory at Luebeck will determine NT-proBNP levels for calculation of the endpoint from samples obtained at baseline and at discharge.	Measured at baseline (within 24 hours of admission to index hospitalization) and on the day of discharge from index hospitalization (discharge planning is at the discretion of treating physician but will be around 5 to 8 days after admission)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with IVC ultrasound on two thirds of days in hospital and at discharge among all randomized patients	Proportion of patients with per-protocol treatment in the experimental group.	Measured on the day of discharge from index hospitalization (discharge planning is at the discretion of treating physician but will be around 5 to 8 days after admission)
All-cause mortality	Participants will be contacted by telephone at 180 days (180 to 210 days) after randomization to assess vital status (all-cause mortality). In case of unavailability patients, relatives, general practitioners, and/or population register will be contacted.	180 days after randomization
Cardiovascular mortality	Participants will be contacted by telephone at 180 days (180 to 210 days) after randomization to assess vital status (all-cause mortality). In case of unavailability patients, relatives, general practitioners, and/or population register will be contacted. Medical reports will be requested to adjudicate cause of death.	180 days after randomization
Unscheduled readmission for any cause	Participants will be contacted by telephone at 180 days (180 to 210 days) after randomization to assess readmission status. In case of unavailability patients, relatives, general practitioners, and/or population register will be contacted.	180 days after randomization
Readmission for heart failure	Participants will be contacted by telephone at 180 days (180 to 210 days) after randomization to assess readmission status. In case of unavailability patients, relatives, general practitioners, and/or population register will be contacted. Medical reports will be requested to adjudicate cause of readmission.	180 days after randomization
Hemoconcentration	Hemoconcentration will be defined as a relative increase in hemoglobin from baseline to discharge.	Measured at baseline (within 24 hours of admission to index hospitalization) and on the day of discharge from index hospitalization (discharge planning is at the discretion of treating physician but will be around 5 to 8 days after admission)
Freedom from signs of congestion at discharge	Freedom from signs of congestion at discharge is defined as the absence of orthopnea, pulmonary rales, and jugular venous distension in conjunction with none or only a trace of edema at discharge.	Measured on the day of discharge from index hospitalization (discharge planning is at the discretion of treating physician but will be around 5 to 8 days after admission)
Cumulative loop diuretic dose during index hospitalization	For calculation of the cumulative loop diuretic dose during index hospitalization all intrahospital applied doses of loop diuretics will be converted to intravenous furosemide equivalents and summed up. Preclinical doses applied by the emergency medical services will not be considered.	Measured on the day of discharge from index hospitalization (discharge planning is at the discretion of treating physician but will be around 5 to 8 days after admission)
Length of index hospitalization	Time in days from hospital admission to hospital dicharge.	Measured on the day of discharge from index hospitalization (discharge planning is at the discretion of treating physician but will be around 5 to 8 days after admission)

Collaborators and Investigators

• Sponsor: University of Luebeck
• Collaborators: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2017
• Primary Completion (Actual): September 24, 2019
• Study Completion (Actual): September 24, 2019

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: May 2, 2017
• First Posted (Actual): May 4, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: heart failure; congestion; acute decompensated heart failure; inferior vena cava
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CAVA-ADHF-DZHK10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No