Effect of Short-Term Prednisone Therapy on C-Reactive Protein Change in Emergency Department Patients With Acute Heart Failure and Elevated Inflammatory Markers ( CORTAHF )

Acute Heart Failure Clinical Trial

— CORTAHF  

Official title:

Effect of Short-Term Prednisone Therapy on C-Reactive Protein Change in Emergency Department Patients With Acute Heart Failure and Elevated Inflammatory Marker

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05668676
• Other study ID #: APHP220428
• Secondary ID: 2022-001604-17
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: February 16, 2023
• Est. completion date: March 2024

Study information

• Verified date: October 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Yonathan FREUND, PU-PH
• Phone: 0184827129
• Email: yonathanfreund[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute heart failure (AHF) is a common discharge diagnosis in the emergency department (ED), associated with 1-month mortality of 6%, and a 30% risk rate of 1-month rehospitalisation. Current guidelines recommend the use of nitrates and low dose diuretics to treat congestion, but to date, no drug has ever shown any improved clinical outcome when given at the acute phase.

Several studies suggest that there is a high inflammatory component in AHF, with elevated markers such as IL6 and C-reactive protein (CRP). As it is the case in other acute respiratory disease, a short course of steroid therapy may limit the inflammatory response and in turn, improve AHF prognosis.

The objective of the study is to assess the effect of a 7-day course of steroid introduced in the ED on inflammatory response

Description:

A multicentric (5 EDs in France), phase 3, comparative, open-label, randomised controlled study in 2 parallel-group comparing usual AHF treatment (control group) with usual AHF treatment + prednisone (intervention group). The objective is to assess the effect of a 7-day course of prednisone therapy started in the ED and continued for up to 7 days on the change of CRP level.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age 18 to 85 years of age

2. Unplanned ED visit within the 12 hours prior to Screening with acute or worsening dyspnea and/or orthopnea, and Pulmonary congestion on chest X-ray or lung ultrasound.

3. All measures from presentation to randomization of systolic blood pressure = 100 mmHg, and of heart rate = 60 bpm.

4. Written informed consent to participate in the study.

5. Affiliation to a french social security system (beneficiary or legal)

6. Biomarker levels indicative of congestion and inflammation: At Screening, NT-proBNP > 1,500 pg/mL or BNP>375 pg/mL and CRP > 40 mg/L

7. Patient agrees for follow-up visit at the hospital at day 7 in case of earlier discharge and Day 30.

Exclusion Criteria:

1. Anticipated life expectancy less than 6 months

2. Mechanical ventilation (not including CPAP/BIPAP) prior to Screening.

3. Significant pulmonary disease contributing substantially to the patients' dyspnea such as FEV1< 1 liter or need for chronic systemic or non- systemic steroid therapy, or any kind of primary right heart failure such as primary pulmonary hypertension or recurrent pulmonary embolism.

4. Myocardial infarction, unstable angina or cardiac surgery within 3 months, or cardiac resynchronization therapy (CRT) device implantation within 3 months, or percutaneous transluminal coronary intervention (PTCI), within 1 month prior to inclusion.

5. Index Event (admission for AHF) triggered primarily by a correctable etiology such as significant arrhythmia (e.g., sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response >130 beats per minute, or bradycardia with sustained ventricular arrhythmia <45 beats per minute), infection, severe anemia, acute coronary syndrome, pulmonary embolism, exacerbation of COPD, planned admission for device implantation or severe non-adherence leading to very significant fluid accumulation prior to admission and brisk diuresis after admission. Troponin elevations without other evidence of an acute coronary syndrome are not an exclusion.

6. Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy.

7. History of heart transplant or on a transplant list, or using or planned to be implanted with a ventricular assist device.

8. Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.

9. Presence at screening of any hemodynamically significant valvular stenosis or regurgitation, except mitral or tricuspid regurgitation secondary to left ventricular dilatation, or the presence of any hemodynamically significant obstructive lesion of the left ventricular outflow tract.

10. Primary liver disease considered to be life threatening (defined by a prothrombin time < 30%)

11. eGFR < 30 mL/min/1.73m2 or eGFR > 80 mL/min/1.73m2 (as estimated by the simplified MDRD formula) at inclusion or history of dialysis.

12. Systemic steroid therapy, within 30 days from inclusion.

13. Inability to consent, or patient under guardianship measure

14. Participation in another intervention trial in the past 30 days

15. Anticipated non-adherence to study protocol or follow-up.

16. Pregnant or nursing (lactating) women.

17. Known hypersensitivity to steroids or constituents of prednisone tablets (excipients)

18. Psychotic states not yet controlled by treatment

19. Concomitant administration of live vaccines and up to 3 months before end of corticotherapy administration

20. Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom

21. Persons subject to psychiatric care without their consent

Related Conditions & MeSH terms

• Acute Heart Failure
• Emergencies
• Heart Failure

Intervention

Drug:
• Prednisone arm
2 tabs of 20 mg prednisone per day during 7 days added to usual care medications

Other:
• Usual care
Usual care alone as per European guidelines, which includes oxygen in case of hypoxia, low dose furosemide (40mg or daily dosage), and iv nitrates if no contra-indication.

Locations

Country	Name	City	State
France	Emergency department Hospital Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CRP value from inclusion to day 7	To assess the effects of prednisone therapy started in the ED and continued for up to 7 days on the change of CRP level.	Day 7
Secondary	The composite of death, or hospital readmission for decompensated HF through day 30 or worsening heart failure occurring between 24h after randomization through the earliest of discharge or day 7		Day 30
Secondary	Comparisons on the effects on change in quality of life	Changes in quality of life measured by the EQ-5D-5L from randomization to day 7	Day 7
Secondary	Comparisons on the effects on change in quality of life	Changes in quality of life measured by the EQ-5D-5L from randomization to Day 30	Day 30
Secondary	Symptoms of heart failure	Changes in symptoms of congestion (NYHA classification, orthopnea, peripheral edema, rales, jugular venous pulse, dyspnea) at day 7	Day 7
Secondary	signs of heart failure	Changes in heart failure signs	Day 7
Secondary	Change in weight from randomization to day 7		Day 7
Secondary	Death from any cause at day 30		Day 30
Secondary	Readmission for HF or death		30 days