This is a global multicenter, doubleblind, placebo-controlled, randomized, parallel-group study that compares ALP-1 given in a continuous infusion ( compared to placebo), 250mcg/day on majore outcomes up to 6 months after randomization in participants with advanced HF with reduced ejection fraction(HFrEF).

We anticipate needing to screen ca. 600 patients in order to ransomize our target sample size of 400 participants. Participants will be randomozed 1:1to receive either alprostadil or placebo. Based on prior data, we expect the 6-month event rate to be 64% in the control group and 47% in the intervention group.

The planned duration of following-up for each patient is 6 months on the randomized trial intervention and a final follow-up visit will be performed 30 days after stopping the trial intervention. Eligible patients will be randomzied via a centralized IXRS to eith alprstadil or placebo. The planned study dusration is approximately 3-4 years from first randomized patient to last patient.

When a participant is deemed eligible to participate in the trial, a central line which will be used for infusion of double-blind treatment will be inserted, if not already in place. Continue infusion delivery system will be operated by a pump.

Infusion of trial intervention will be initiated while the participant is in the hospital of infusion centre and the participant is to remain under observation for at least 8 hours for monitoring of vital signs and adverse event(AEs).

1. Patients older than 18 years of age, of any gender/sex and race/ethnicity

2. Patients with a diagnosis of advanced HFrEF as evidenced by (all must apply):

   1. most recent LVEF( by conventional imaging method<30% which was mwasured within 3 months prior randomization.
   2. Nt-proBNP >1500 ng/L or BNP >300 ng/L at prior randomization
   3. New York Heart Association (NYHA) functional class IIIb or IV, i.e., chronic dyspnoea or fatigue at rest or with minimal exertion for at least one month prior to consent.
   4. Renal dysfunction reflected by a glomerular filtration rate (GFR) <60 mL/min approximated by the Modification of Diet in Renal Disease formula.
   5. A total symptom score of KCCQ of <70measure within 24 hours of randomization
   6. Patients on all appropriate recommended HF therapy.

3. Patient should not be receiving continuous or planned intermittent intravenous infusions with a positive inotropic or vasodilator drug in a non-hospitalized setting

4. Patients should not be considered as candidates for heart transplantation or LVAD for at least 6 months from randomization according to the opinion of the treating physician.

5. Women of childbearing potential (i.e., who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must commit either to abstain continuously from heterosexual sexual contact or to use at least one "highly effective" method of birth control (e.g., intrauterine device [IUD], hormonal contraception, tubal ligation, or partner's vasectomy) or two "effective" methods (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to screening and throughout study participation.

   Note: As alprostadil is not genotoxic and female sexual partners of male study participants are not likely to have substantial exposure via semen, there are no contraception requirements for men.

6. Patients must be willing and able to give written informed consent, including local data privacy consents, as required

The party or parties involved in the study trials who are prevented from having knowledge of the interventions assigned to individual participants