NCT03734211

Brief Summary

The main goal of this study is to evaluate the effect of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac allograft vasculopathy in de novo heart transplant recipients. Secondary objectives are to assess the impact of treatment on: i) cholesterol levels, ii) renal function, iii) inflammation, iv) quality of life, v) cardiac function as assessed by biomarkers and echocardiography, vi) the number of rejections, and (vii) safety and tolerability. As an exploratory outcome, the investigators will asses the effect of treatment on clinical events (death, myocardial infarction, cerebral stroke, cancer, end stage renal disease).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
130

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2019

Typical duration for phase_3

Geographic Reach
3 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 26, 2018

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 7, 2018

Completed
7 months until next milestone

Study Start

First participant enrolled

June 10, 2019

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 20, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2023

Completed
Last Updated

November 1, 2023

Status Verified

October 1, 2023

Enrollment Period

3.9 years

First QC Date

October 26, 2018

Last Update Submit

October 30, 2023

Conditions

Cardiac Allograft Vasculopathy

Keywords

EvolocumabHeart TransplantationVasculopathy

Outcome Measures

Primary Outcomes (1)

  • Maximal intimal thickness

    The maximal intimal thickness will be measured by coronary intravascular ultrasound at 12 months after randomization. The maximal intima thickness is defined as the largest distance (in mm) from the intimal leading edge to the external elastic membrane.

    12 months

Secondary Outcomes (13)

  • Cardiac allograft vasculopathy

    12 months

  • Total atheroma volume

    12 months

  • The index of microvascular resistance

    12 months

  • Low-density lipoprotein (LDL) cholesterol

    12 months

  • Estimated glomerular filtration rate (eGFR)

    12 months

  • +8 more secondary outcomes

Study Arms (2)

Evolocumab

EXPERIMENTAL

Evolocumab (Repatha®) will be administered subcutaneously once monthly in the abdomen, thigh, or upper arm for the duration of the treatment period (one year). The 420 mg evolocumab/placebo will be administered by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.

Drug: Evolocumab

Placebo

PLACEBO COMPARATOR

The placebo is presented in an identical prefilled autoinjector. It is supplied as a sterile, single-use, preservative-free solution for subcutaneous injection in a disposable, spring-based prefilled autoinjector. The prefilled autoinjector contains a 1.0 mL deliverable volume of 1.1% (w/v) sodium carboxymethylcellulose, 250 mM proline, 10 mM acetate, and 0.01% (w/v) polysorbate 80, pH 5.0.

Drug: Placebo

Interventions

EvolocumabDRUG

420 mg evolocumab will be administered subcutaneously by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.

Also known as: Repatha
Evolocumab
PlaceboDRUG

Placebo will be administered subcutaneously by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.

Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients will be screened for eligibility during routine follow-up 4 - 8 weeks after heart transplantation. All of the following conditions must apply prior to administering the investigational medicinal product:
  • Heart transplant recipient within the last 4 - 8 weeks.
  • Age between 18 and 70 years.
  • Informed consent obtained and documented according to Good Clinical Practice (GCP), and national/regional regulations.
  • No contraindications to coronary angiography with intravascular ultrasound
  • Estimated glomerular filtration rate \> 20 ml/min/1.73 m2 as assessed by the MDRD formula.

You may not qualify if:

  • Patients will be excluded from the study if they meet any of the following criteria:
  • Decompensated liver disease (Child-Pugh class C)
  • Severe renal failure, i.e. eGFR \< 20 ml/min/1.73 m2 or on renal replacement therapy
  • Ongoing rejections or infections
  • Known sensitivity or intolerance to evolocumab or any of the excipients of Repatha®
  • Prior use of PCSK9 inhibition treatment
  • Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake
  • Participation in another clinical trial involving an investigational drug and/or follow-up within 30 days prior to enrolment.
  • Pregnancy.
  • Female subject who has either (1) not used at least one highly effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilised or postmenopausal.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Department of Cardiology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Department of Cardiology, Aarhus University Hospital

Skejby, 8200, Denmark

Location

Helsinki University Hospital Heart and Lung Center

Helsinki, 00029, Finland

Location

Department of Cardiology, Sahlgrenska University Hospital

Gothenburg, SE-41345, Sweden

Location

The Clinic for Heart Failure and Valvular Disease, Skåne University Hospital and Lund University

Lund, 22185, Sweden

Location

Related Publications (2)

  • Broch K, Lemstrom KB, Gustafsson F, Eiskjaer H, Karason K, Gjesdal G, Fagerland MW, Pentikainen M, Lommi J, Gude E, Andreassen AK, Clemmensen TS, Christiansen EH, Bjorkelund E, Berg ES, Arora S, Gullestad L. Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients. JACC Heart Fail. 2024 Oct;12(10):1677-1688. doi: 10.1016/j.jchf.2024.04.026. Epub 2024 Jun 26.

    PMID: 38934968DERIVED

  • Broch K, Gude E, Karason K, Dellgren G, Radegran G, Gjesdal G, Gustafsson F, Eiskjaer H, Lommi J, Pentikainen M, Lemstrom KB, Andreassen AK, Gullestad L. Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients: Design of the randomized controlled EVOLVD trial. Clin Transplant. 2020 Sep;34(9):e13984. doi: 10.1111/ctr.13984. Epub 2020 Aug 6.

    PMID: 32445429DERIVED

MeSH Terms

Conditions

Vascular Diseases

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Study Officials

  • Lars Gullestad, MD, PhD

    Oslo University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

October 26, 2018

First Posted

November 7, 2018

Study Start

June 10, 2019

Primary Completion

May 20, 2023

Study Completion

May 20, 2023

Last Updated

November 1, 2023

Record last verified: 2023-10

Locations

DK(2)FI(1)SE(2)