Hearth Failure With Reduced Ejection Fraction (HFrEF)Phase 4PARASAILNCT02690974
Description of Tolerability of LCZ696 (Sacubitril / Valsartan) in Heart Failure With Reduced Ejection Fraction (HFrEF) Treated in Real Life Setting
A Phase 4 study testing LCZ696 (sacubitril/valsartan) in people with Hearth Failure With Reduced Ejection Fraction (HFrEF), run by Novartis Pharmaceuticals at 32 sites in Canada.
Trial summary
The primary purpose of the study was to describe the tolerability of treatment with the optimal dose of LCZ696 (97 mg sacubitril / 103 mg valsartan bid), over six (6) months, in patients with heart failure with reduced ejection fraction (HFrEF) in Canada. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hearth Failure With Reduced Ejection Fraction (HFrEF)
- What is being tested?
- LCZ696 (sacubitril/valsartan)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 32 sitesCanada
- Study dates
- 8 Mar 2016to 29 Nov 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Written informed consent must be obtained before any assessment is performed.
- Age ≥ 18 years and ≤ 80 years.
- Males or females.
- Diagnosis of Heart Failure NYHA class II-III.
- Diagnosis of Heart Failure with reduced Ejection Fraction (LVEF =< 40%) and NYHA class II or III.
- Stable on any dose of ACEI or ARB prior to enrolment in the study
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- Stable on any dose of a beta-blocker prior to enrolment in the study.
- Eligible for treatment with LCZ696 as per Canadian product monograph.
- Treated as an outpatient.
- Signed an informed consent agreeing to participate in the study.
Who cannot join
- Symptomatic hypotension and/or a SBP < 100 mmHg at baseline visit.
- Estimated GFR < 30 mL/min/1.73m^2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at baseline visit.
- Known history of angioedema related to previous ACEI or ARBs therapy, or history of hereditary or idiopathic angioedema.
- Requirement of concomitant treatment with both ACEIs and ARBs.
- Concurrent participation in other clinical trials or receiving other investigational drugs within 30 days of enrollment.
- Hypersensitivity to the active substances, sacubitril or valsartan, or to any of the excipients.
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- Concomitant use of aliskiren-containing drugs in patients with diabetes mellitus (type 1 or type 2) or moderate to severe renal impairment (GFR <60ml/min/1.73m^2).
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods are described in the protocol.
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
Canada32 sites
Novartis Investigative Site
Brossard, J4Z 2K9
Novartis Investigative Site
Burlington, Ontario, L7M 4Y1
Novartis Investigative Site
Cambridge, Ontario, N1R 6V6
Novartis Investigative Site
Edmonton, Alberta, T5H 3V9
Novartis Investigative Site
Greater Sudbury, Ontario, P3E 3B8
Novartis Investigative Site
Greater Sudbury, Ontario, P3E 5M9
Novartis Investigative Site
Greenfield Park, Quebec, J4V 2G8
Novartis Investigative Site
Hamilton, L8L 0A9
Novartis Investigative Site
Joliette, Quebec, J6E 6J2
Novartis Investigative Site
London, Ontario, N6A 5A5
Novartis Investigative Site
Mississauga, Ontario, L5K 2L3
Novartis Investigative Site
Moncton, New Brunswick, E1C 2Z3
Novartis Investigative Site
Moncton, New Brunswick, E1G 1A7
Novartis Investigative Site
Montreal, Quebec, H1T 3Y7
Novartis Investigative Site
New Westminster, British Columbia, V3L 3W4
Novartis Investigative Site
Newmarket, Ontario, L3Y 2P6
Novartis Investigative Site
Newmarket, Ontario, L3Y 8C3
Novartis Investigative Site
Ottawa, Ontario, K1Y 4W7
Novartis Investigative Site
Peterborough, Ontario, K9J 0B2
Novartis Investigative Site
Québec, GIV 4G5
Novartis Investigative Site
Saint-Jean-sur-Richelieu, Quebec, J3A 1J2
Novartis Investigative Site
Saint-Lambert, J4P 2J2
Novartis Investigative Site
Sarnia, Ontario, N7T 4X3
Novartis Investigative Site
Scarborough Village, Ontario, M1E 5E9
Novartis Investigative Site
Scarborough Village, Ontario, M1P 2V5
Novartis Investigative Site
St. John's, Newfoundland and Labrador, A1B 3V6
Novartis Investigative Site
Terrebonne, Quebec, J6V 2H2
Novartis Investigative Site
Toronto, Ontario, M6R 1B5
Novartis Investigative Site
Vancouver, British Columbia, V6Z 1Y6
Novartis Investigative Site
Waterloo, Ontario, N2T 0C1
Novartis Investigative Site
Weston, Ontario, M9N 1W4
Novartis Investigative Site
Winnipeg, Manitoba, R2H 2A6
About this study
Official title: Prospective, Multi-center, Open lAbel, Post-appRovAl Study AImed at Characterizing the Use of LCZ696 at 97 mg Sacubitril / 103 mg Valsartan Bid in Patients With HFrEF
The primary purpose of the study was to describe the tolerability of treatment with the optimal dose of LCZ696 (97 mg sacubitril / 103 mg valsartan bid), over six (6) months, in patients with heart failure with reduced ejection fraction (HFrEF) in Canada.
The study was also to describe the overall tolerability, effectiveness and safety of LCZ696 for the management of HFrEF over 12 months of treatment, as well as describe the patterns of LCZ696 up and down dose titrations occurring during the management of patients with HFrEF.
- Being tested
- LCZ696 (sacubitril/valsartan)
- Keywords
- HFrEF,, ACEi,, ACE inhibitor,, ARBs,, systolic heart failure,, chronic heart failure,, CHF,, reduced EF,, Ejection Fraction
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCZ696 (sacubitril/valsartan)Drug
All patients were treated with the LCZ696 (sacubitril and valsartan) tablets
| Study group | Role | What they receive |
|---|---|---|
| LCZ696 (sacubitril / valsartan) | Other | All patients were initiated on either LCZ696 at 24 mg sacubitril / 26 mg valsartan or LCZ696 at 49 mg sacubitril / 51 mg valsartan bid for 2-4 weeks and were up-titrated to the next higher dose for another 2 - 4 weeks as applicable. Receives: Drug: LCZ696 (sacubitril/valsartan) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants on LCZ696 200 mg Bid at Month 6
The tolerability of LCZ696 was defined as the percentage of patients on LCZ696 at the dose of 97 mg sacubitril / 103 mg valsartan twice daily (bid) who did not experience down titration or treatment discontinuation because of adverse events while on this dose at month 6. Only descriptive analysis done.
Measured: Month 6
Secondary outcomes (7)
Percentage of Participants on LCZ696 200 mg Bid at Month 12
The tolerability of LCZ696 was defined as the percentage of patients on LCZ696 at the dose of 97 mg sacubitril / 103 mg valsartan twice daily (bid) who did not experience down titration or treatment discontinuation because of adverse events while on this dose at month 12. Only descriptive analysis done.
Measured: Month 12
Percentage of Participants Requiring Down-titration From LCZ696 200 mg
The impact of the titration scheme on the tolerability of patients maintained on LCZ696 97 mg sacubitril / 103 mg valsartan bid was defined as the percentage of patients on LCZ696 200mg requiring down-titration. Only descriptive analysis done.
Measured: Month 12
Percentage of Participants With Down-titration Changes From LCZ696 200 mg During 12 Months of Treatment
The impact of the titration scheme on the tolerability of patients maintained on LCZ696 97 mg sacubitril / 103 mg valsartan bid was defined as the number of down-titration during the 12 months treatment period. Dow-titration schemes considered for the analysis are 200 mg to 100 mg; 100 mg to 50 mg; and 50 mg to 0 mg (i.e. treatment discontinuation). The down-titration scheme of 50mg to 0 mg was taken in account in this analysis to ensure to reflect all actual changes in dose. Only descriptive analysis done.
Measured: Month 12
Change From Baseline in the Six Minute Walk Test (6MWT) at Month 6 and Month 12
The impact of LCZ696 on functional exercise capacity was measured by the Six Minute Walk Test at 6 and 12 months. The 6MWT measures the distance an individual is able to walf over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. Only descriptive analysis done.
Measured: Baseline, Month 6 and Month 12
Time to Each Up-titration to LCZ696 100 mg and LCZ696 200 mg
To describe the time of up-titration for each dose (24 mg sacubitril / 26 mg valsartan bid and 49 mg sacubitril / 51 mg valsartan bid) of LCZ696. Only descriptive analysis done.
Measured: Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
Median Time to Reach LCZ696 200 mg
To describe the time of up-titration for each dose (24 mg sacubitril / 26 mg valsartan bid and 49 mg sacubitril / 51 mg valsartan bid) of LCZ696. Only descriptive analysis done.
Measured: Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
Percentage of Participants on Guideline Recommended Dose of Beta-blockers and MRAs Over Time
To describe the adherence to guideline recommended dosing of beta-blockers and MRAs at 6 and 12 months of treatment of LCZ696. Only descriptive analysis done.
Measured: Baseline, Month 6 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study start8 Mar 2016
- Primary completion7 Jun 2017
- Study completion29 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hearth Failure With Reduced Ejection Fraction (HFrEF)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02690974
- Sponsor's protocol ID
- CLCZ696BCA02
- Acronym
- PARASAIL
- Status last verified
- Mar 2019
- First submitted
- 15 Feb 2016
- Last updated
- 7 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multi-center, Open lAbel, Post-appRovAl Study AImed at Characterizing the Use of LCZ696 at 97 mg Sacubitril / 103 mg Valsartan Bid in Patients With HFrEF
- ClinicalTrials.gov ID
- NCT02690974
- Acronym / sponsor ID
- PARASAIL / CLCZ696BCA02
- Keywords
- HFrEF,, ACEi,, ACE inhibitor,, ARBs,, systolic heart failure,, chronic heart failure,, CHF,, reduced EF,
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2016 (actual)
- Primary completion
- 7 Jun 2017 (actual)
- Study completion
- 29 Nov 2017 (actual)
- First posted
- 24 Feb 2016 (estimated)
- Results
- Posted 7 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the study was to describe the tolerability of treatment with the optimal dose of LCZ696 (97 mg sacubitril / 103 mg valsartan bid), over six (6) months, in patients with heart failure with reduced ejection fraction (HFrEF) in Canada.
The study was also to describe the overall tolerability, effectiveness and safety of LCZ696 for the management of HFrEF over 12 months of treatment, as well as describe the patterns of LCZ696 up and down dose titrations occurring during the management of patients with HFrEF.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LCZ696 (sacubitril / valsartan) | Other | Drug: LCZ696 (sacubitril/valsartan)All patients were initiated on either LCZ696 at 24 mg sacubitril / 26 mg valsartan or LCZ696 at 49 mg sacubitril / 51 mg valsartan bid for 2-4 weeks and were up-titrated to the next higher dose for another 2 - 4 weeks as applicable. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent must be obtained before any assessment is performed.
- Age ≥ 18 years and ≤ 80 years.
- Males or females.
- Diagnosis of Heart Failure NYHA class II-III.
- Diagnosis of Heart Failure with reduced Ejection Fraction (LVEF =< 40%) and NYHA class II or III.
Key exclusion criteria (11 listed)
- Symptomatic hypotension and/or a SBP < 100 mmHg at baseline visit.
- Estimated GFR < 30 mL/min/1.73m^2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at baseline visit.
- Known history of angioedema related to previous ACEI or ARBs therapy, or history of hereditary or idiopathic angioedema.
- Requirement of concomitant treatment with both ACEIs and ARBs.
- Concurrent participation in other clinical trials or receiving other investigational drugs within 30 days of enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LCZ696 (sacubitril/valsartan)All patients were treated with the LCZ696 (sacubitril and valsartan) tablets | Drug | LCZ696 (sacubitril / valsartan) |
Primary outcome
Percentage of Participants on LCZ696 200 mg Bid at Month 6
Time frame: Month 6
The tolerability of LCZ696 was defined as the percentage of patients on LCZ696 at the dose of 97 mg sacubitril / 103 mg valsartan twice daily (bid) who did not experience down titration or treatment discontinuation because of adverse events while on this dose at month 6. Only descriptive analysis done.
7 secondary outcomes
Percentage of Participants on LCZ696 200 mg Bid at Month 12
Time frame: Month 12
Percentage of Participants Requiring Down-titration From LCZ696 200 mg
Time frame: Month 12
Percentage of Participants With Down-titration Changes From LCZ696 200 mg During 12 Months of Treatment
Time frame: Month 12
Change From Baseline in the Six Minute Walk Test (6MWT) at Month 6 and Month 12
Time frame: Baseline, Month 6 and Month 12
Time to Each Up-titration to LCZ696 100 mg and LCZ696 200 mg
Time frame: Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
Median Time to Reach LCZ696 200 mg
Time frame: Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
Percentage of Participants on Guideline Recommended Dose of Beta-blockers and MRAs Over Time
Time frame: Baseline, Month 6 and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing LCZ696 (sacubitril/valsartan) in people with Hearth Failure With Reduced Ejection Fraction (HFrEF), run by Novartis Pharmaceuticals at 32 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants on LCZ696 200 mg Bid at Month 6 (time frame: Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2019.