PARADISE-MI: PROSPECTIVE ARNI VERSUS ACE INHIBITOR TRIAL TO DETERMINE SUPERIORITY IN REDUCING HEART FAILURE EVENTS AFTER MYOCARDIAL INFARCTION

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-047-16
• Date of registration: 16/02/2017
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS BIOSCIENSES PERU S.A.,
• Public title: PARADISE-MI: PROSPECTIVE ARNI VERSUS ACE INHIBITOR TRIAL TO DETERMINE SUPERIORITY IN REDUCING HEART FAILURE EVENTS AFTER MYOCARDIAL INFARCTION
• Scientific title: A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, PARALLEL-GROUP PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF LCZ696 COMPARED TO RAMIPRIL ON MORBIDITY AND MORTALITY IN HIGH RISK PATIENTS FOLLOWING AN ACUTE MYOCARDIAL INFARCTION
• Date of first enrolment: 20/04/2017
• Target sample size: 60
• Recruitment status: Recruiting
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=047-16
• Study type: Interventional
• Study design: This study is a multicenter, randomized, double-blind, active controlled, event-driven phase III clinical trial designed to evaluate the efficacy and safety of LCZ696 compared to ramipril when added to standard therapy in post-AMI patients with LV systolic dysfunction and/or pulmonary congestion over a period of approximately 32 months.; A screening period, or epoch, of no more than 7 days after index MI presentation will be used; to determine if patients qualify to enter the double-blind treatment phase of the study. Eligible patients will be randomized 1:1 to receive LCZ696 titrated to a target dose of 200 mg twice daily or ramipril titrated to a target dose of 5 mg twice daily.; The study is event-driven and will continue until the requirement of total confirmed endpoint events, i.e., 800 primary composite endpoint events and 633 CV death or HF hospitalization events, has been achieved.
• Phase: III

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, China, Germany, Greece, Italy, Mexico, Netherlands, Peru, Portugal, United States

Contacts

• Name: Cecilia Ynouye
• Affiliation: NOVARTIS BIOSCIENCES PERU S.A.

• Name: Cecilia Ynouye
• Affiliation: NOVARTIS BIOSCIENCES PERU S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent.
2. At least18 years of age.
3. Diagnosis of spontaneous AMI with randomization to occur between 12 hours and 7 days after index event presentation.
4. Evidence of LV systolic dysfunction and/or pulmonary congestion requiring intravenous treatment associated with the index MI event.
5. At least one of the 8 risk factors: Age ≥ 70 years, eGFR <60 mL/min/1.73 m2, Type I or II diabetes mellitus, history of prior MI supported by ECG changes and/or elevation of
cardiac enzymes, atrial fibrillation, LVEF <30% associated with index MI, worst Killip class III or IV associated with index MI requiring intravenous treatment, STEMI without reperfusion therapy within the first 24 hours after presentation
6. Hemodynamically stable.

Exclusion criteria:
1 History of chronic HF prior to randomization.
2 Cardiogenic shock within 24h prior to randomization.
3 Persistent clinical HF at the time of randomization.
4 Coronary artery bypass graft.
5. Clinically significant right ventricular MI as index MI.
6. Symptomatic hypotension.
7 History of angioedema.
8. Stroke or transient ischemic attack 1 month prior to randomization.
9. Known or suspected bilateral renal artery stenosis.
10. Clinically significant obstructive cardiomyopathy.
11. Open-heart surgery 1 month prior to randomization or planned cardiac surgery within the 3 months after randomization.
12. eGFR < 30 ml/min/1.73 m2 at V1.
13. Serum potassium > 5.2 mmol /L at V1.
14. Known hepatic impairment or history of cirrhosis.
15 Previous use of LCZ696.
16 Other investigational drugs 30 days prior to V1.
17 Hypersensitivity to the study drugs.
18 Intolerance to study drugs.
19 Taking medications prohibited by the protocol.
20 History of malignancy of any organ system.
21 Medical condition at investigators’ discretion.
22 Drug or alcohol abuse.
23 Patients considered unsuitable for the study.
24 Pregnant or nursing.
25 Women of child-bearing potential unless using highly effective methods of contraception.


Age minimum:
Age maximum:
Gender: --

Health Condition(s) or Problem(s) studied

-I50

I50

Intervention(s)

All eligible patients will be randomized 1:1 to either LCZ696 titrated to a target dose of 200 mg twice daily or ramipril titrated to a target dose of 5 mg twice daily in a double-blind manner for the duration of the study.
LCZ696: 50 mg (level 1), 100 mg (level 2) and 200 mg (level 3) twice daily (oral). LCZ696 levels are equivalent to sacubitril/valsartan 24/26 mg, 49/51 mg and 97/103 mg, respectively.
Ramipril: 1.25 mg (level 1), 2.5 mg (level 2), and 5 mg (level 3) twice daily (oral).
Valsartan (VAL489): 40 mg (V1) and 80 mg (V2) twice daily for one day (oral). Patients who are randomized to LCZ696 and received ACE inhibitors in last 36 hours prior to randomization will be given a valsartan bridging in a blinded manner for one day with two doses at dose level V1 or V2: 40 or 80 mg twice daily, prior to beginning the double-blind LCZ696 treatment.

Source(s) of Monetary Support

NOVARTIS BIOSCIENSES PERU S.A.

Ethics review

Status: Approved
Approval date: 14/10/2016
Contact:

[e-mail]

Hospital Nacional Guillermo Almenara Irigoyen - EsSalud

999436950

[e-mail]

Status: Approved
Approval date: 18/10/2016
Contact:

[e-mail]

Hospital Nacional Arzobispo Loayza

88339014 - 3301677

[e-mail]

Status: Approved
Approval date: 22/08/2017
Contact:

[e-mail]

Hospital Nacional Hipolito Unanue

99686880

[e-mail]

Results

• Results available: Yes
• Date Completed: 27/01/2021