Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD (EARLY-MYO-CTD)

January 4, 2020 updated by: RenJi Hospital

Effect of Sacubitril/Valsartan on Right Ventricular Dysfunctioning Patients With Connective Tissue Disease

Heart failure, one of the leading causes of connective tissue disease (CTD) mortality, has attracted increasing attention. Currently, no known study had focused on the effect of sacubitril/valsartan on right ventricular dysfunction and in the systemic disease induced heart disease. We aimed to observe the effect of sacubitril/valsartan on primary endpoints (6 minutes walking test and myocardial fibrosis) in CTD patients with right ventricular ejection fraction reduction (RV-HFrEF).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Patients with CTD frequently exhibit multi-organ pathophysiological and functional damage. Heart failure, one of the leading causes of CTD mortality, has attracted increasing attention. Mostly, patients with CTD present with nonspecific cardiac symptoms, normal ECG, and preserved left ventricular ejection fraction (LVEF) and therefore do not receive an early cardiac diagnosis and treatment. Pulmonary arterial hypertension (PAH), right ventricular (RV) dilatation and hypertrophy might become the first and the most frequent cardiac findings. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitors, is a "superstar" which inhibits both neprilysin and renin-angiotensin aldosterone system that closely related to the heart failure mechanism. It has been strongly recommended as class I drug in treating the patient with chronic HFrEF from 2017 ACC/AHA/HFSA heart failure guideline for the ability of dramatically reduce the cardiovascular mortality rate.

Cardiovascular magnetic resonance (CMR) is able to depict myocardial characteristics from structure to tissue properties using cine and late gadolinium enhancement (LGE) sequences. Newly developed imaging studies to date include T1 mapping and T1-derived extracellular volume estimation. All the previous studies in CTD have been restricted to patients with advanced cardiac involvement.

Together with clinical assessment and multi-imaging tests, the aim of the present study is going to observe the effect of sacubitril/valsartan on primary endpoints (6 minutes walking test and myocardial fibrosis) in CTD patients with RV-HFrEF.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • RenJi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age between 18-75 years old.
  • confirmed CTD（including systemic lupus erythematosus, myositis, polymyositis, systemic sclerosis, sarcoid, Sjögren's syndrome or mixed connective tissue disease）
  • SLEDAI ≤ 6 in patients with SLE or ESR ≤ 30 in patients with SSc
  • already have OPT for CTD at least 3 month
  • RVEF ≤ 45%
  • Providing written informed consent

Exclusion Criteria:

  • Documented coronary artery disease or prior angiography for coronary artery disease (>50% stenosis).
  • Patients with known congenital heart disease or other systemic diseases that might induce RVrEF.
  • Patients with standard metallic contraindications to CMR or an estimated glomerular filtration rate < 30 ml/min/1.73 m2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: sacubitril/valsartan group
The diagnosis of CTD was made based on the clinical classification criteria. The patient was diagnosed by an echocardiography demonstration, when RVEF is suggested lower or equal to 45%, the patient will be considered a candidate after consent is signed. sacubitril/valsartan will be given.
Drug: Sacubitril / Valsartan Oral Tablet
After recruiting participants and collecting the baseline information, sacubitril/valsartan group will receive sacubitril/valsartan and optimal pharmaceutical treatment (OPT). The control group will receive valsartan and OPT. A CMR scan and a post-processed imaging procedure will later be carried on in order to detect the cardiac impairment.
Other Names:
  • CMR examination
NO_INTERVENTION: control group
The diagnosis of CTD was made based on the clinical classification criteria. The patient was diagnosed by an echocardiography demonstration, when RVEF is suggested lower or equal to 45%, the patient will be considered a candidate after consent is signed. Valsartan will be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exercise tolerance
Time Frame: change between 1 and 6 months after treatment
6 minutes walking test
change between 1 and 6 months after treatment
Fibrosis Assessment
Time Frame: change between 1 and 6 months after treatment
LGE assessment
change between 1 and 6 months after treatment
Fibrosis Assessment
Time Frame: change between 1 and 6 months after treatment
ECV quantification
change between 1 and 6 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CTD activity
Time Frame: change between 1 and 6 months after treatment
antinuclear antibody
change between 1 and 6 months after treatment
Cardiovascular Mortality Rate
Time Frame: change between 1 and 6 months after treatment
all cause of death
change between 1 and 6 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RenJi Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

February 20, 2020

Primary Completion (ANTICIPATED)

November 1, 2022

Study Completion (ANTICIPATED)

November 1, 2022

Study Registration Dates

First Submitted

November 27, 2019

First Submitted That Met QC Criteria

December 10, 2019

First Posted (ACTUAL)

December 12, 2019

Study Record Updates

Last Update Posted (ACTUAL)

January 7, 2020

Last Update Submitted That Met QC Criteria

January 4, 2020

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-11-01R

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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