Antihypertensive Effect of Different Doses of Rostafuroxin in Comparison With Losartan

NCT03217825 | Completed Phase 2 DMC

• 1 other identifier: CVT-CV-001
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The principal aim of the study is to demonstrate that Rostafuroxin is able to induce a more pronounced reduction of arterial blood pressure respect to Losartan, in hypertensive patients carrying at least one of the pre-specified gene mutations. In previous studies has been demonstrated that these mutations are able to induce specific alterations inducing an increase of sodium (Na) reabsorption at renal tubular level and an increase of arterial blood pressure. Pilot studies have demonstrated that Rostafuroxin is able to reduce the impact of these alterations, and so directly reverse the increase in blood pressure.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Systolic Blood Pressure

  Automated sitting and standing SBP and DBP will be recorded by physician at baseline (two visits) and at week 2, 5 and 9 of treatement. sitting: after the patient has rested for at least 10 minutes in a quiet room. There are five consecutive sitting BP readings with a 30 to 60 seconds interval between the readings; the mean of the last three sitting BP will be used.

  Week 9 of treatment versus baseline

Secondary Outcomes (3)

• Diastolic blood pressure

  Baseline (two visits) and then at week 2, 5 and 9 of treatment

• Trough-to-peak ratio on Systolic Blood Pressure

  Throughout 24 hours ABPM

• Number of participants with adverse events

  throughout all the study period and follow-up (30 days)

Study Arms (4)

Rostafuroxin 6 micrograms capsules

EXPERIMENTAL

1 capsule of ROSTAFUROXIN (6 micrograms) once a day before breakfast.

Drug: Rostafuroxin

Rostafuroxin 50 micrograms capsules

EXPERIMENTAL

1 capsule of ROSTAFUROXIN (50 micrograms) once a day before breakfast.

Drug: Rostafuroxin

Rostafuroxin 500 micrograms

EXPERIMENTAL

1 capsule of ROSTAFUROXIN (500 micrograms) once a day before breakfast.

Drug: Rostafuroxin

Losartan 50 mg encapsulated

ACTIVE COMPARATOR

1 capsule containing one cpr of Losartan 50 mg once a day before breakfast.

Drug: Losartan

Interventions

Rostafuroxin DRUG

This is a potent, selective and safe inhibitor of this altered mechanism and has been proved to be effective in reducing blood pressure levels in Adducin mutated rat strains and in chronic Ouabain infused rat model.

Also known as: Rosta

Rostafuroxin 50 micrograms capsules; Rostafuroxin 500 micrograms; Rostafuroxin 6 micrograms capsules

Losartan DRUG

COZAAR (losartan potassium) is an angiotensin II receptor (type AT1) antagonist. Losartan potassium, a nonpeptide molecule, is chemically described as 2-butyl-4-chloro-1-\[p-(o-1H-tetrazol-5-ylphenyl)benzyl\]imidazole- 5-methanol monopotassium salt.

Losartan 50 mg encapsulated

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signature of a written informed consent, included informed consent on genotype analysis.
• Naive hypertensive patient (new diagnosed patient, never treated before).
• Documented mild to moderate arterial hypertension: SBP comprised between 140 and 169 mmHg and DBP between 85 and 100 mmHg;
• Presence of at least one mutated genotype or combination of genotypes corresponding to the list provided in the protocol.

You may not qualify if:

• Known causes of secondary or severe or malignant hypertension;
• Significant renal or hepatic disease;
• Cardiac disease requiring prohibited pharmacological treatment or history of myocardial infarction within the last 6 months;
• Atrial Fibrillation or Complete Ventricle Bundle Branch Block;
• First degree AV-block exceeding 240 msec;
• Electrocardiographic evidence of left ventricular hypertrophy;
• Pregnant or nursing women or women of childbearing potential not taking anti-contraceptive medication or not utilizing a double contraceptive method;
• Concomitant therapy with medications that may affect blood pressure;
• Diabetes mellitus (fasting plasma glucose \> 125 mg/dl);
• Statins treatment.

Sponsors & Collaborators

• Windtree Therapeutics: lead

Study Sites (1)

Cvie Therapeutics Limited

Taipei, 100, Taiwan

Location

Related Publications (1)

• Citterio L, Bianchi G, Scioli GA, Glorioso N, Bigazzi R, Cusi D, Staessen JA, Cavuto S, Ferrandi M, Lanzani C, Li X, Lau LF, Chiang CE, Wang TD, Wang KL, Ferrari P, Manunta P. Antihypertensive treatment guided by genetics: PEARL-HT, the randomized proof-of-concept trial comparing rostafuroxin with losartan. Pharmacogenomics J. 2021 Jun;21(3):346-358. doi: 10.1038/s41397-021-00214-y. Epub 2021 Mar 1.

  PMID: 33649520 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

rostafuroxin; Losartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Bianchi Giuseppe, MD

  CVie Therapeutics Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 14, 2017
• Study Start: December 1, 2015
• Primary Completion: February 8, 2018
• Study Completion: February 8, 2018
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)