DESAL-HEART: Hypertonic Saline Added to a Pre-declared Furosemide Dose in Acute Heart Failure (DESAL-HEART)
DESAL-HEART is a multicenter, randomized, open-label, blinded-endpoint, mechanistic proof-of-concept trial conducted within the Heart Failure Efficacy and Research Trial (HEART) Platform. The study will evaluate whether adding a single infusion of 3% hypertonic saline solution (HSS) to a pre-declared intravenous furosemide dose improves decongestion in patients hospitalized with acute heart failure.
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
Background and Rationale
Congestion is a major cause of hospitalization in patients with acute heart failure. Intravenous loop diuretics, such as furosemide, are the standard treatment for removing excess fluid, but treatment responses vary and residual congestion remains common.
Hypertonic saline may temporarily increase effective circulating blood volume, improve kidney perfusion, and enhance the delivery and effectiveness of furosemide. Although previous studies have suggested potential benefits, limitations in study quality and differences in treatment regimens have prevented definitive conclusions.
DESAL-HEART is designed to isolate the effect of hypertonic saline by ensuring that the furosemide dose is determined before randomization and administered in both treatment groups.
Study Design
A total of 60 adults hospitalized with acute heart failure and persistent congestion will be randomized in a 1:1 ratio to receive either:
A single 150 mL infusion of 3% hypertonic saline administered over 30 minutes together with a pre-declared intravenous furosemide dose; or
The same pre-declared intravenous furosemide dose alone.
Randomization will be performed centrally using REDCap, with stratification by chronic kidney disease status. The study is open-label because the control group will not receive a placebo infusion. Laboratory endpoints will be assessed objectively.
The treating clinician will determine and document the intravenous furosemide dose before randomization. Subsequent heart failure management will remain at the discretion of the treating physician.
Study Objectives and Assessments
The primary objective is to estimate the effect of hypertonic saline on NT-proBNP, a biomarker of heart failure, measured 24 ± 6 hours after randomization.
The key mechanistic secondary endpoint is spot urine sodium concentration measured 90-150 minutes after randomization, providing an early measure of the kidneys' response to diuretic treatment.
Additional assessments include:
NT-proBNP at 48 ± 6 hours after randomization.
Spot urine sodium from the first urine sample collected more than 6 hours after randomization.
Changes in body weight, hemoglobin, hematocrit, serum electrolytes, and creatinine at 24 hours.
Urine output, net fluid balance, and additional decongestive treatments during the first 24 hours.
Treatment delivery, recruitment feasibility, and completeness of outcome assessments.
Safety assessments will include infusion intolerance, clinically important electrolyte abnormalities, changes in kidney function, symptomatic hypotension, worsening respiratory status, and serious adverse events. A serum sodium increase of at least 5 mmol/L from baseline or any sodium value of at least 150 mmol/L is a prespecified adverse event of special interest.
Exploratory outcomes include major adverse kidney events and days alive and out of hospital at 30 days. Additional clinical and patient-reported outcomes will be collected through the HEART Platform.
Statistical Analysis and Study Purpose
The primary analysis will use a mixed model for repeated measures to compare log-transformed NT-proBNP at 24 and 48 hours between treatment groups, adjusting for baseline NT-proBNP, site, chronic kidney disease status, age, and sex. The treatment effect will be reported as a geometric mean ratio with a 95% confidence interval.
This 60-participant study is intended to estimate the magnitude and precision of the biological treatment effect rather than establish clinical efficacy. A prespecified Green/Yellow/Red decision framework will integrate the biological signal, urine sodium response, safety, and feasibility to determine whether further investigation in a definitive clinical outcomes trial is warranted.
Type d'étude
Inscription (Estimé)
Phase
- Phase 4
Contacts et emplacements
Coordonnées de l'étude
- Nom: Justin Ezekowitz, MD
- Numéro de téléphone: 780-492-0712
- E-mail: jae2@ualberta.ca
Sauvegarde des contacts de l'étude
- Nom: Fernando G Zampieri, MD,PhD
- Numéro de téléphone: 587-588-6151
- E-mail: fzampier@ualberta.ca
Lieux d'étude
-
-
Alberta
-
Edmonton, Alberta, Canada
- University of Alberta
-
Contact:
- Fernando G Zampieri, MD, PhD
- Numéro de téléphone: 587-588-6151
- E-mail: fzampier@ualberta.ca
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
-
Adults aged 18 years or older.
-
Primary diagnosis of acute heart failure with dyspnea and at least two of the following signs of congestion:
- Pulmonary congestion on chest radiograph.
- Rales on chest auscultation.
- Clinically relevant peripheral edema.
- Elevated jugular venous pressure.
-
Randomization within 24 hours of the hospital admission order or admitted status, with admission to a hospital ward or intensive care unit, including patients remaining in the emergency department awaiting transfer.
-
Persistent congestion with a clinical plan for another intravenous furosemide dose.
-
NT-proBNP ≥1000 pg/mL, regardless of the presence of atrial fibrillation.
-
Estimated glomerular filtration rate (eGFR) >15 mL/min/1.73 m².
-
Serum sodium ≥125 mmol/L and <145 mmol/L.
-
Meets the eligibility requirements of the HEART Platform Master Protocol.
Exclusion Criteria:
- Hypertonic saline already administered during the current presentation.
- A clinical indication for therapeutic hypertonic saline.
- Contraindication to either study treatment, including known allergy, hypersensitivity, or intolerance to hypertonic saline or furosemide.
- Requirement for mechanical circulatory support.
- Dialysis-dependent kidney failure or anuria (absence of urine production).
- Treating physician's judgment that either treatment strategy is inappropriate, or any condition that, in the opinion of the investigator, would make participation unsafe or interfere with interpretation of study results.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Hypertonic Saline Plus Furosemide
Participants will receive a single 150 mL intravenous infusion of 3% hypertonic saline over 30 minutes, administered concurrently with a pre-declared intravenous furosemide dose. The furosemide dose will be determined by the treating clinician before randomization. Subsequent treatment will follow standard clinical care. |
A single 150 mL intravenous infusion of 3% sodium chloride (hypertonic saline solution) administered over 30 minutes, initiated at the same time as the pre-declared intravenous furosemide dose. A single intravenous dose of furosemide determined and documented by the treating clinician before randomization. The same pre-declared dosing approach applies to both treatment groups. Subsequent diuretic treatment is determined by the treating physician according to standard clinical care. |
|
Comparateur actif: Furosemide Alone
Participants will receive a pre-declared intravenous furosemide dose without hypertonic saline. The furosemide dose will be determined by the treating clinician before randomization using the same dosing approach as the intervention group. Subsequent treatment will follow standard clinical care. |
A single intravenous dose of furosemide determined and documented by the treating clinician before randomization. The same pre-declared dosing approach applies to both treatment groups. Subsequent diuretic treatment is determined by the treating physician according to standard clinical care. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change From Baseline in NT-proBNP at 24 Hours
Délai: Baseline to 24 hours after randomization
|
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to 24 hours after randomization. NT-proBNP is a blood biomarker of heart failure. |
Baseline to 24 hours after randomization
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Spot Urine Sodium Concentration at 90-150 Minutes
Délai: 90-150 minutes after randomization
|
Spot urine sodium concentration measured 90-150 minutes after randomization to assess the early natriuretic response to intravenous furosemide with or without hypertonic saline. |
90-150 minutes after randomization
|
|
Change From Baseline in NT-proBNP at 48 Hours
Délai: Baseline to 48 hours after randomization
|
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to 48 hours after randomization to assess the persistence of the treatment effect on this heart failure biomarker |
Baseline to 48 hours after randomization
|
|
Spot Urine Sodium Concentration at 6 Hours
Délai: First urine void more than 6 hours after randomization
|
Spot urine sodium concentration measured from the first urine sample collected more than 6 hours after randomization to assess the sustained natriuretic response to treatment. The actual sample collection time will be recorded. |
First urine void more than 6 hours after randomization
|
|
Change From Baseline in Hemoglobin at 24 Hours
Délai: Baseline and 24 hours after randomization
|
Change in blood hemoglobin concentration from baseline to 24 hours after randomization, measured using routine complete blood count testing. |
Baseline and 24 hours after randomization
|
|
Change From Baseline in Hematocrit at 24 Hours
Délai: Baseline and 24 hours after randomization
|
Change in hematocrit from baseline to 24 hours after randomization, measured using routine complete blood count testing |
Baseline and 24 hours after randomization
|
|
Change From Baseline in Body Weight at 24 Hours
Délai: Baseline and 24 hours after randomization
|
Change in body weight from baseline to 24 hours after randomization to assess fluid removal and decongestion. |
Baseline and 24 hours after randomization
|
|
Total Urine Output Through 24 Hours
Délai: Randomization through 24 hours
|
Total recorded urine output during the first 24 hours after randomization to assess the diuretic response to treatment. |
Randomization through 24 hours
|
|
Net Fluid Balance Through 24 Hours
Délai: Randomization through 24 hours
|
Net fluid balance, calculated as total recorded fluid intake minus total recorded fluid output during the first 24 hours after randomization. |
Randomization through 24 hours
|
|
Total Furosemide-Equivalent Dose Through 24 Hours
Délai: Randomization through 24 hours
|
Total furosemide-equivalent diuretic dose administered during the first 24 hours after randomization, including the pre-declared study dose and subsequent diuretic treatments. |
Randomization through 24 hours
|
|
Other Decongestive Therapies Through 24 Hours
Délai: Randomization through 24 hours
|
Use of additional decongestive therapies during the first 24 hours after randomization, including treatments administered at the discretion of the treating physician. |
Randomization through 24 hours
|
|
Change From Baseline in Serum Sodium
Délai: Baseline and 24 hours
|
Change in serum sodium concentration from baseline to 24 hours after randomization. |
Baseline and 24 hours
|
|
Change From Baseline in Serum Chloride
Délai: Baseline and 24 hours
|
Change in serum chloride concentration from baseline to 24 hours after randomization. |
Baseline and 24 hours
|
|
Change From Baseline in Serum Potassium
Délai: Baseline and 24 hours
|
Change in serum potassium concentration from baseline to 24 hours after randomization. |
Baseline and 24 hours
|
|
Change From Baseline in Serum Bicarbonate
Délai: Baseline and 24 hours
|
Change in serum bicarbonate concentration from baseline to 24 hours after randomization. |
Baseline and 24 hours
|
|
Change From Baseline in Serum Creatinine
Délai: Baseline and 24 hours
|
Change in serum creatinine concentration from baseline to 24 hours after randomization to assess kidney function. |
Baseline and 24 hours
|
Collaborateurs et enquêteurs
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Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Effets physiologiques des drogues
- Agents natriurétiques
- Composés de soufre
- Produits chimiques organiques
- Préparations pharmaceutiques
- Actions pharmacologiques
- Actions et utilisations chimiques
- Amides
- Composés aniline
- Amines
- Produits chimiques inorganiques
- Composés de chlore
- Solutions
- Sulfonamides
- Sulfanilamides
- Sulfones
- Composés de sodium
- Chlorures
- Acide chlorhydrique
- Solutions hypertoniques
- Furosémide
- Diurétiques
- Chlorure de sodium
- Solution saline, hypertonique
Autres numéros d'identification d'étude
- DESAL-01
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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