HypercholesterolemiaPhase 4NCT04397653
Evolocumab Plus Ezetimibe in High Risk Haemodialized Statin Intolerant Patients
A Phase 4 study testing Evolocumab and Ezetimibe in people with Hypercholesterolemia and Chronic Kidney Disease Requiring Chronic Dialysis, run by Policlinico Casilino ASL RMB at 1 site in Italy.
Trial summary
Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol, reducing in turn the risk of cardiovascular events. Whether evolcumab is effective in haemodialized patients is uncertain. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypercholesterolemia, Chronic Kidney Disease Requiring Chronic Dialysis
- What is being tested?
- Evolocumab and Ezetimibe
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 4 May 2020to 14 Dec 2020
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- high cardiovascular risk defined as patients with: Documented cardiovascular disease (CVD), clinical or unequivocal on imaging. Documented clinical CVD includes previous acute myocardial infarction, coronary revascularization and other arterial revascularization procedures, stroke and TIA, aortic aneurysm and PAD. Unequivocally documented CVD on imaging includes plaque on coronary angiography or carotid ultrasound; DM with target organ damage or with a major risk factor such as smoking or marked hypercholesterolaemia or marked hypertension.
- History of statin intolerance, demonstrated by both:
- trial of ≥2 statins with intolerance of any dose or to increase statin dose above the total maximum doses because of intolerable: Myopathy or myalgia (muscle pain, ache, or weakness without CK elevation), or Myositis (muscle symptoms with increased CK levels), or Rhabdomyolysis (muscle symptoms with marked CK elevation) and Resolution or improvement of symptoms when the statin dose was decreased or discontinued
- patients with LDL-C ≥70 mg/dL
- end-stage renal disease on chronic hemodialysis
Who cannot join
- LDL-C <70 mg/dL
- NYHA class III-IV heart failure or last known LVEF <30%
- Uncontrolled serious cardiac arrhythmia, defined as recurrent and highly symptomatic VT, AF with rapid ventricular response, or SVT that are not controlled by medications, within 3 months prior to randomization Planned cardiac surgery or revascularization DM, including: Type 1 DMType 2 DM that is poorly controlled (HbA1c>8.5%) or newly diagnosed within 6 months before randomization; Laboratory evidence of DM during screening (fasting serum glucose ≥126 mg/dL [7.0 mmol/L] or HbA1c≥6.5%) without prior DM diagnosis
- Uncontrolled hypertension, defined as sitting SBP >160mmHg or DBP>100 mm Hg
- Use during the 6 months before LDL-C screening of red yeast rice, niacin >200 mg/d, prescription lipid-regulating drugs (eg, fibrates or derivatives) other than statins, ezetimibe, bile-acid sequestrants, stanols, or stanol esters
- Use during the 12 months before LDL-C screening of a CETP inhibitor such as anacetrapib, dalcetrapib, or evacetrapib
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- Use during the 3 months before LDL-C screening of systemic cyclosporine, systemic steroids excluding HRT, vitamin A derivatives (excluding vitamin Ain a multivitamin), or retinol derivatives for the treatment of dermatologic conditions
- Laboratory values at screening TSH < LLN or >1.5 × ULN; CK >3 × ULN; AST or ALT >2 × ULN
- Known concurrent illness within 3 months
- Infection
- Major hematologic, renal, metabolic, GI, or endocrine dysfunction in the judgment of the investigator
- DVT or PE
- Pregnancy, breastfeeding, or inadequate birth control in premenopausal female subjects
- Previous treatment with evolocumab or any other anti-PCSK9 therapy
- Inability to provide informed consent or to attend follow-up visits
- Unreliability as a study participant based on judgment of investigator's knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, psychosis)
- Current enrollment in another investigational device or drug study or <30 d since ending another investigational device or drug study
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Policlinico Casilino
Rome, 00169
Leonardo Calò, MD, 0623188406, leonardocalo.doc@gmail.com
Luca Monzo, MD, PhD, 00393460242037, luca.monzo@uniroma1.it
About this study
Official title: Phase IV Study for Efficacy and Safety of Evolocumab Added to Ezetimibe (Standard of Care) in High Cardiovascular Risk Haemodialized Statin Intolerant Patients With Hypercholesterolemia
Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol, reducing in turn the risk of cardiovascular events. Whether evolcumab is effective in haemodialized patients is uncertain. The investigators will conduct a randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab in high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia. Patients will be randomly assigned to receive evolocumab (140 mg subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) or matching placebo (subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) for 24 weeks. The primary efficacy end point will be the reduction in LDL-C ≥ 20 mg/dL from baseline. The key secondary efficacy end points will be: the reduction of LDL-C from baseline at 4, 6 and 12 weeks; the reduction of HDL-C, non-HDL cholesterol and triglycerides from baseline at 24 weeks; the number of patients achieving LDL-C <70 mg/dL. Every adverse event (serious and non-serious) correlated to drug infusion will be recorded (safety end-point).
- Being tested
- Evolocumab, Placebo, Ezetimibe
- Keywords
- PCSK9 inhibitor, Evolocumab, End-stage renal disease, Hypercholesterolemia, Low-density lipoprotein
- Medical subject headings
- Hypercholesterolemia, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
In the intervention arm evolocumab 140 mg subcutaneous every 2 weeks will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia
PlaceboDrug
In the placebo arm placebo subcutaneous every 2 weeks will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia
EzetimibeDrug
Ezetimibe 10 mg daily will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia in both the placebo arm (plus placebo) and in the intervention arm (plus evolocumab)
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab + Ezetimibe | Experimental | Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks Receives: Drug: Evolocumab; Drug: Ezetimibe |
| Placebo + Ezetimibe | Placebo comparator | Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks Receives: Drug: Placebo; Drug: Ezetimibe |
What is being measured
The primary outcome is the main question the study is designed to answer.
LDL cholesterol reduction dichotomic
change in LDL cholesterol levels ≥ 20 mg/dL from baseline
Measured: 24 weeks
Secondary outcomes (5)
LDL cholesterol reduction time-points
change in LDL cholesterol levels from baseline
Measured: 4 weeks, 12 weeks, 24 weeks
HDL cholesterol reduction
change in HDL cholesterol levels from baseline
Measured: 24 weeks
non-HDL cholesterol reduction
change in non-HDL cholesterol levels from baseline
Measured: 24 weeks
Triglycerides reduction
change in triglycerides levels from baseline
Measured: 24 weeks
LDL cholesterol target achieving
percent of patients achieving an LDL cholesterol less than 70 mg/dL
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2020
- Study start4 May 2020
- Primary completion19 Nov 2020 (estimated)
- Study completion14 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Policlinico Casilino ASL RMB
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS San Raffaele
- Responsible party
- Principal investigator, Leonardo Calò, MD, Policlinico Casilino ASL RMB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04397653
- Sponsor's protocol ID
- Evolocumab01
- Status last verified
- May 2020
- First submitted
- 12 May 2020
- Last updated
- 26 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.
PubMed 24694531Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R. 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25.
PubMed 27712954Expert Dyslipidemia Panel; Grundy SM. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia. J Clin Lipidol. 2013 Nov-Dec;7(6):561-5. doi: 10.1016/j.jacl.2013.10.001. Epub 2013 Oct 22.
PubMed 24314355Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvanne M, Scholte op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F; European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012 Jul;33(13):1635-701. doi: 10.1093/eurheartj/ehs092. Epub 2012 May 3. No abstract available.
PubMed 22555213