Paroxysmal Atrial FibrillationPhase 3RESTORE-1NCT05039359
Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation
A Phase 3 study testing FlecIH-103 in people with Paroxysmal Atrial Fibrillation, run by InCarda Therapeutics, Inc. at 40 sites in 6 countries.
Trial summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of FlecIH-103 (flecainide acetate inhalation solution) compared with placebo in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Paroxysmal Atrial Fibrillation
- What is being tested?
- FlecIH-103
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 40 sitesin 6 countries
- Study dates
- 26 Apr 2022to 22 May 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 and ≤85 years of age
- Recent onset of symptomatic newly diagnosed or paroxysmal AF
- Recent onset is defined as a symptom duration ≥1 and ≤48 hours at time of dosing
- Newly diagnosed AF is AF that has not been diagnosed previously, independent of its duration
- Paroxysmal AF is defined as recurrent AF in a patient whose previous AF episode(s) self-terminated (ie, without treatment) or terminated with intervention ≤7 days of onset.
- A symptomatic recent-onset AF episode post cardiac ablation for paroxysmal AF would be considered eligible
Who cannot join
- History of non self-terminating AF/AFL as defined by
- One or more failed attempts to restore SR with pharmacological therapy
- ECV procedure for an AF episode ≤1 year prior to screening. Exception: One (1) prior ECV is allowed if no option for pharmacological conversion was previously available
- More than 3 ECV procedures in ≤5 years prior to screening
- Current diagnosis of persistent AF
- Persistent AF defined as AF that is continuously sustained >7 days, including episodes terminated by cardioversion (drugs or electrical cardioversion) after >7 days. Patients with persistent AF do not have self-terminating AF episodes
Show all 69Show fewer
- Patients who have undergone an ablation procedure for persistent AF are not eligible
- One or more episodes of AFL ≤6 months prior to randomization
- Exception: a patient who has received ablation for AFL ≤3 months prior to screening with no recurrence of AFL prior to randomization is considered eligible Vital signs
- Hemodynamic or cardiac instability during AF, defined as any of the following:
- Systolic blood pressure <100 or ≥160 mmHg
- Diastolic blood pressure ≥95 mmHg
- Ventricular heart rate <80 or >160 bpm
- Respiratory rate >22 breaths per minute Relevant structural heart disease
- History of decompensated heart failure (HF)
- Evidence of significant HF defined as any of the following:
- Hospitalization in the last 12 months for HF or suspected HF event b. Most recent assessment of left ventricular ejection fraction (LVEF) <45% i. For patients in the United States, a standard diagnostic echocardiogram assessed ≤180 days prior to screening is required to ascertain eligibility. If none is available, the patient must undergo a standard diagnostic echocardiogram or a diagnostic echocardiogram using a portable ultrasound device (handheld echocardiogram [HHE]) during screening to confirm eligibility c. New York Heart Association (NYHA) Class II-IV symptoms d. Medication history suggestive of HF per the Investigator's discretion
- Signs or symptoms of ongoing myocardial ischemia, including any of the following:
- Significant ST segment elevation or depression (ie, ≥2 mm) on a standard 12-lead ECG
- Echocardiogram findings (eg, wall motion abnormalities) suggestive of acute myocardial infarction (MI)
- Angina pectoris, atypical angina pectoris, or receiving antianginal medication for ischemia
- History of MI ≤3 months of screening
- History of uncorrected moderate or severe aortic or mitral valvular stenosis, in the opinion of the Investigator
- If an echocardiogram is performed at screening, moderate or severe valve disease observed during the examination is considered exclusionary
- History of LV hypertrophy with LV thickness >12 mm as observed in the most recent assessment, ie, an echocardiogram Other CV conditions
- Stroke (including transient ischemic attack) ≤3 months prior to randomization
- History of any of the following cardiac abnormalities:
- Long QT syndrome
- Conduction system disease (eg, PR interval >200 ms, second- or third degree heart block, bundle branch block)
- Brugada syndrome
- Torsade de pointes
- Diagnosed with sinus node dysfunction (eg, sick sinus syndrome) or any of the following:
- History of unexplained or cardiovascular syncope ii. Bradycardia suggestive of sinus node dysfunction iii. Prior electrical or pharmacological cardioversion associated with sinus or ventricular pause >3 seconds or ventricular heart rate <45 bpm at time of conversion
- Any of the following ECG-related features at screening:
- QT interval corrected for heart rate using the Fridericia formula (QTcF) >480 msec
- Wide QRS complex (ie, duration ≥120 msec) or history of documented wide QRS complex tachycardia (ie, wide QRS complex with ventricular heart rate >100 bpm)
- Presence of ventricular tachycardia (VT). Site telemetry should be equipped with an alarm system for VT and PVCs or be continuously visually observed prior to dosing
- Presence of a pacemaker
- Cardiac surgery for any of the exclusionary conditions (eg, valvular disease, hypertrophy, coronary artery disease) ≤6 months prior to randomization Prior and concomitant non-CV conditions
- Known severe renal impairment or patient receiving dialysis
- Known abnormal liver function, including hepatic disease or biochemical evidence of significant liver derangement
- Uncorrected hypokalemia
- Hypokalemia is defined as serum potassium below the normal range according to the local laboratory reference ranges at screening
- If serum potassium is below the normal range at screening, therapeutic correction (eg, potassium supplementation) is required
- Uncorrected hypomagnesemia
- Hypomagnesemia is defined as serum magnesium below the normal range according to the local laboratory reference ranges at screening
- If serum magnesium result is below the normal range at screening, therapeutic correction (eg, magnesium supplementation) is required
- Chronic obstructive pulmonary disease or other established pulmonary disease in need of inhalation medication
- Exception: patients with intermittent mild asthma who are not experiencing active symptoms at screening, and whose asthma is well controlled with as-needed administration of a bronchodilator ≤2 days/week, and who has not experienced ≥2 exacerbations requiring oral systemic corticosteroids ≤1 year prior to screening
- History of bronchospasm (eg, hyperreactive airways to inhalants) or difficulty inhaling medications
- Previous or current hospitalization for COVID-19, or any secondary cardiomyopathy from COVID-19 Prior and concomitant medications and procedures
- Treatment with Class I or III AADs ≤7 days prior to randomization
- Treatment with amiodarone ≤12 weeks prior to randomization
- Known hypersensitivity to flecainide acetate, any active metabolites of flecainide acetate, or any excipients in FlecIH-103
- Any condition or circumstance which in the opinion of the Investigator may make the patient unsuitable for the study, such as:
- High risk for stroke based on the screening coagulation panel or medical history per Investigator's discretion (eg, CHA2DS2-VASc score)
- Congenital heart disease
- AF that is secondary to electrolyte imbalance, thyroid disease, or other reversible or non-cardiovascular cause
- A serious or life-threatening medical condition
- An acute infection
- Known drug or alcohol dependence ≤12 months prior to screening as judged by the Investigator
- A body mass index ≥35 kg/m2
- Legally incompetent to provide informed consent
- Previous treatment with any other investigational drug ≤30 days from screening or 5 half-lives of the drug, whichever is longer
- Female of childbearing potential defined as any of the following:
- Not surgically sterile or postmenopausal (Appendix 1)
- A negative pregnancy test is unavailable at screening
- Pregnant or breastfeeding at screening
- Males whose sexual partners are women of childbearing potential (WOCBP) must use at least one highly effective method of contraception during the study unless permenantly sterile by bilateral orchiectomy.
Trial locations and contacts
40 sites in 6 countries.
40 sites in 6 countries
United States18 sites
Bridgeport Hospital
Bridgeport, Connecticut, 06610
University of Cincinnati College of Medicine
Cincinnati, Ohio, 45267
The MetroHealth System
Cleveland, Ohio, 44109
Cleveland Clinic Emergency Department
Cleveland, Ohio, 44195
UC Davis Medical Center
Davis, California, 95819
North Kansas City Hospital
Kansas City, Kansas, 64116
University of Kansas Medical Center Research Institute
Kansas City, Kansas, 66160
Memorial Care
Long Beach, California, 90806
IU Health Ball Memorial Hospital
Muncie, Indiana, 47303
Mount Sinal Hospital
New York, New York, 10019
Weill Cornell Medical Center
New York, New York, 10021
Saint Michaels Medical Center
Newark, New Jersey, 07102
Orlando Health Heart and Vascular Institute and Orlando Regional medical Center
Orlando, Florida, 32806
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Reading Hospital
Reading, Pennsylvania, 19611
Reid Physician Associates
Richmond, Indiana, 47374
The Valley Hospital, Inc
Ridgewood, New Jersey, 07450
Tampa General Hospital; Center of Research Excellence
Tampa, Florida, 33606
Netherlands8 sites
Deventer Ziekenhuis
Deventer, 7417 SE
Ziekenhuis Gelderse Vallei
Ede, 6716RP
Admiraal de Ruyter Ziekenhuis
Goes, 4462 RA
Universitair Medisch Centrum Groningen (UMCG)
Groningen, 9713 GZ
Spaarne Gasthuis
Haarlem, 2035 RC
Medisch Centrum Leeuwarden
Leeuwarden, 8934 AD
Diakonessenhuis
Utrecht, 3582 KE
Maxima Medisch Centrum
Veldhoven, 5504 DB
Spain8 sites
Hospital General Universitario de Alicante
Alicante, 3010
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Hospital Ramon y Cajal
Madrid, 28034
Fundacion Jimenez Diaz
Madrid, 28040
La Paz Univerisity Hospital
Madrid, 28046
Hospital Universitario Puera de Hierro
Madrid, 28222
Fundacion Hospital Son Liatzer
Palma de Mallorca, 7198
Hospital Santiago De Compostela
Santiago de Compostela, 15706
Hungary2 sites
DPC Hospital Egyesitett Szent Istvan es Szent Laszlo Korhaz
Budapest, 1097
University of PACs
Pécs, 7624
Poland2 sites
Mazowiecki Szpital Specjalistyczny w Ostrolece
Ostrołęka, 07-410
Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
Torun, 87-100
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial of Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of FlecIH-103 (flecainide acetate inhalation solution) compared with placebo in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Approximately 400 patients are expected to be enrolled in this study. Patients will be randomized 3:1 to receive FlecIH-103 at a total dose of up to 120 mg estimated total lung dose (eTLD) (n=300) or placebo inhalation solution (n=100). Randomization will be stratified by geographic region (US and ex-US) and duration of symptoms of the current AF episode (≥1 hour to ≤24 hours and >24 hours to ≤48 hours).
Read the detailed description
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of FlecIH-103 (flecainide acetate inhalation solution) compared with placebo in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Approximately 400 patients are expected to be enrolled in this study. The study will consist of the following periods: Screening, Observation, and Follow-up.
The Screening Period comprises the time from the patient signing informed consent to the time of randomization. Screening begins at least 45 minutes prior to dosing and may be extended as needed due to site logistics. During screening, the patient will be evaluated for study eligibility, have a standard triplicate 12-lead ECG to confirm the diagnosis of AF, have a single-lead patch electrode applied for continuous ECG (cECG) recording, undergo a targeted physical examination (including cardiovascular and respiratory systems), have blood drawn for laboratory assessments and a predose pharmacokinetic (PK) sample, have their AF-related symptoms assessed, have vital signs assessed periodically, and be monitored via telemetry to ensure they remain predominantly in AF prior to dosing (ie, no period of SR ≥1 minute in duration or any abnormal rhythm other than AF). After confirmation that the patient meets all applicable eligibility criteria, randomization will take place using a central randomization system. The patient is considered enrolled at the time of randomization.
The Observation Period comprises the time from randomization through 90 minutes after initiation of dosing. After randomization and just prior to the start of dosing (T0), the patient's AF will again be confirmed by a standard triplicate 12-lead ECG; patients who are not in AF at this time must be withdrawn. The patient will inhale the study drug until conversion of AF to SR occurs for ≥1 minute or the complete dose is administered, whichever occurs first. The complete dose of study drug comprises 2 separate 3.5-minute inhalations separated by a 1-minute break. Telemetric recording of ECG and cECG monitoring will continue and vital signs will be monitored periodically. A PK sample will be collected 2 minutes after completion of dosing followed by another standard triplicate ECG collected 5 minutes after completion of dosing. Finally, AF-related symptoms will be checked and a final PK sample will be collected at 90 minutes after initiation of dosing. Wherever a time point requires collection of ECG and/or vital signs in addition to a PK sample, the PK sample is collected last.
If the patient's AF converts to SR (sustained for ≥1 minute) as observed on telemetry during the Observation Period, vital signs and a standard triplicate 12-lead ECG will be recorded immediately following the time of conversion. The Investigator may not offer the patient another rhythm control therapy to cardiovert their AF to SR until after 90 minutes after initiation of dosing. At the end of the Observation Period (ie, 90 minutes after initiation of dosing), the cECG patch will be removed and a standard triplicate 12 lead ECG will be recorded. If the patient's AF converts to SR (sustained for ≥1 minute) after the Observation Period but prior to discharge (eg, due to ECV or other PCV), a standard triplicate 12-lead ECG will be recorded at the time of conversion.
The patient may be discharged per the Investigator's discretion any time after completion of the 90-minute time point assessments. If patient discharge occurs >1 hour after completion of the last 90-minute time point assessment, all 90-minute time point assessments must be repeated just prior to discharge, excluding the PK sample.
The Follow-Up Period consists of 2 follow-up telephone contacts: one at 24 (+12) hours after initiation of dosing, and one at 96 (±24) hours after initiation of dosing. The patient will also be given contact information and be instructed to contact the clinic in the event that any AF-related symptoms occur before these scheduled contact times. Follow-up contacts may also be performed by video call or in-person if the patient is at the clinic. During each follow-up contact, the patient will be queried for concomitant medications and procedures, AEs, AF-related symptoms, and AF-related interventions. End of study coincides with the 96-hour follow-up contact.
An independent Data Monitoring Committee (DMC) will monitor safety throughout the study. An independent Clinical Events Committee (CEC) will review blinded data to adjudicate the primary and several secondary efficacy endpoints and to adjudicate CV events of special interest (ie, hypotension, ventricular tachycardia, bradycardia, sinus pause, atrial flutter with 1:1 conduction, and other arrhythmias).
- Conditions
- Paroxysmal Atrial Fibrillation
- Being tested
- FlecIH-103
- Keywords
- atrial fibrillation
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlecIH-103Drug
flecainide acetate inhalation solution
| Study group | Role | What they receive |
|---|---|---|
| FlecIH-103 (flecainide acetate inhalation solution) | Active comparator | Up to two 3.5-minute inhalations separated by a 1-minute break, for a total duration of up to 8 minutes on Day 1. Dosing will continue until conversion of AF to SR is observed for ≥1 minute or the full dose (120 mg eTLD) is administered, whichever occurs first. Receives: Drug: FlecIH-103 |
| Vehicle-matched inhalation solution (placebo) | Placebo comparator | Up to two 3.5-minute inhalations separated by a 1-minute break, for a total duration of up to 8 minutes on Day 1. Receives: Drug: FlecIH-103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of proportion of patients whose AF converts using continuous ECG monitoring
To compare the efficacy of flecainide acetate inhalation solution and placebo for the conversion of atrial fibrillation (AF) to sinus rhythm (SR) in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Conversion from AF to SR will be monitored via continuous ECG recording. The efficacy of flecainide acetate solution and placebo will be compared using conversion as recorded on the ECG.
Measured: 90 minutes
Secondary outcomes (5)
Time of conversion to be monitored using continuous ECGs
To compare the effects of flecainide acetate inhalation solution and placebo on the time to conversion of AF to SR. Conversion from AF to SR will be monitored via continuous ECG recording. The time of conversion as captured on the continuous ECG will be compared between flecainide acetate inhalation solution and placebo.
Measured: 90 minutes
Assessing and comparing the AF related symptoms by using a questionnaire
To compare the effects of flecainide acetate inhalation solution and placebo on the AF-related symptoms. The AF-related symptoms will be reported by the patients in the AF-Related Symptoms Questionnaire at 90 minutes after initiation of dosing.
Measured: 90 minutes post dose
Assessing and comparing the hospital admissions between the active vs. placebo
To compare the effects of flecainide acetate inhalation solution and placebo on the patient hospitalizations prior to discharge as reported by the investigator in the CRF.
Measured: 90 minutes
Assessing and comparing the AF-related interventions prior to discharge between the active vs. placebo
To compare the effects of flecainide acetate inhalation solution and placebo on the AF-related interventions as reported by the investigator in the CRF.
Measured: 90 minutes
Assessing and comparing the time of discharge
To compare the effects of flecainide acetate inhalation solution and placebo on the time to discharge as reported by the investigator in the CRF.
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2021
- Study start26 Apr 2022
- Primary completion22 May 2023
- Study completion22 May 2023
Why it stopped: Limited efficacy upon blinded review
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Atrial FibrillationStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- InCarda Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Luiz Belardinelli, MD, Study director, InCarda Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05039359
- Sponsor's protocol ID
- FLE-007
- Acronym
- RESTORE-1
- Status last verified
- Oct 2023
- First submitted
- 9 Aug 2021
- Last updated
- 30 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rienstra M, Woite-Silva AC, Kuijper A, Eijsbouts S, Kraaier K, Janota T, Van Ofwegen C, Tuininga Y, Badings E, Merino JL, Ruskin JN, Camm AJ, Kowey PR, Dufton C, Maupas J, Parsell D, Belardinelli L. Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial. Europace. 2025 Mar 28;27(4):euaf064. doi: 10.1093/europace/euaf064.
PubMed 40132102
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial of Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm
- ClinicalTrials.gov ID
- NCT05039359
- Acronym / sponsor ID
- RESTORE-1 / FLE-007
- Conditions
- Paroxysmal Atrial Fibrillation
- Keywords
- atrial fibrillation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Limited efficacy upon blinded review
- Enrolment
- 54 participants (actual)
- Lead sponsor
- InCarda Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Apr 2022 (actual)
- Primary completion
- 22 May 2023 (actual)
- Study completion
- 22 May 2023 (actual)
- First posted
- 9 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of FlecIH-103 (flecainide acetate inhalation solution) compared with placebo in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Approximately 400 patients are expected to be enrolled in this study. Patients will be randomized 3:1 to receive FlecIH-103 at a total dose of up to 120 mg estimated total lung dose (eTLD) (n=300) or placebo inhalation solution (n=100). Randomization will be stratified by geographic region (US and ex-US) and duration of symptoms of the current AF episode (≥1 hour to ≤24 hours and >24 hours to ≤48 hours).
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of FlecIH-103 (flecainide acetate inhalation solution) compared with placebo in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Approximately 400 patients are expected to be enrolled in this study. The study will consist of the following periods: Screening, Observation, and Follow-up.
The Screening Period comprises the time from the patient signing informed consent to the time of randomization. Screening begins at least 45 minutes prior to dosing and may be extended as needed due to site logistics. During screening, the patient will be evaluated for study eligibility, have a standard triplicate 12-lead ECG to confirm the diagnosis of AF, have a single-lead patch electrode applied for continuous ECG (cECG) recording, undergo a targeted physical examination (including cardiovascular and respiratory systems), have blood drawn for laboratory assessments and a predose pharmacokinetic (PK) sample, have their AF-related symptoms assessed, have vital signs assessed periodically, and be monitored via telemetry to ensure they remain predominantly in AF prior to dosing (ie, no period of SR ≥1 minute in duration or any abnormal rhythm other than AF). After confirmation that the patient meets all applicable eligibility criteria, randomization will take place using a central randomization system. The patient is considered enrolled at the time of randomization.
The Observation Period comprises the time from randomization through 90 minutes after initiation of dosing. After randomization and just prior to the start of dosing (T0), the patient's AF will again be confirmed by a standard triplicate 12-lead ECG; patients who are not in AF at this time must be withdrawn. The patient will inhale the study drug until conversion of AF to SR occurs for ≥1 minute or the complete dose is administered, whichever occurs first. The complete dose of study drug comprises 2 separate 3.5-minute inhalations separated by a 1-minute break. Telemetric recording of ECG and cECG monitoring will continue and vital signs will be monitored periodically. A PK sample will be collected 2 minutes after completion of dosing followed by another standard triplicate ECG collected 5 minutes after completion of dosing. Finally, AF-related symptoms will be checked and a final PK sample will be collected at 90 minutes after initiation of dosing. Wherever a time point requires collection of ECG and/or vital signs in addition to a PK sample, the PK sample is collected last.
If the patient's AF converts to SR (sustained for ≥1 minute) as observed on telemetry during the Observation Period, vital signs and a standard triplicate 12-lead ECG will be recorded immediately following the time of conversion. The Investigator may not offer the patient another rhythm control therapy to cardiovert their AF to SR until after 90 minutes after initiation of dosing. At the end of the Observation Period (ie, 90 minutes after initiation of dosing), the cECG patch will be removed and a standard triplicate 12 lead ECG will be recorded. If the patient's AF converts to SR (sustained for ≥1 minute) after the Observation Period but prior to discharge (eg, due to ECV or other PCV), a standard triplicate 12-lead ECG will be recorded at the time of conversion.
The patient may be discharged per the Investigator's discretion any time after completion of the 90-minute time point assessments. If patient discharge occurs >1 hour after completion of the last 90-minute time point assessment, all 90-minute time point assessments must be repeated just prior to discharge, excluding the PK sample.
The Follow-Up Period consists of 2 follow-up telephone contacts: one at 24 (+12) hours after initiation of dosing, and one at 96 (±24) hours after initiation of dosing. The patient will also be given contact information and be instructed to contact the clinic in the event that any AF-related symptoms occur before these scheduled contact times. Follow-up contacts may also be performed by video call or in-person if the patient is at the clinic. During each follow-up contact, the patient will be queried for concomitant medications and procedures, AEs, AF-related symptoms, and AF-related interventions. End of study coincides with the 96-hour follow-up contact.
An independent Data Monitoring Committee (DMC) will monitor safety throughout the study. An independent Clinical Events Committee (CEC) will review blinded data to adjudicate the primary and several secondary efficacy endpoints and to adjudicate CV events of special interest (ie, hypotension, ventricular tachycardia, bradycardia, sinus pause, atrial flutter with 1:1 conduction, and other arrhythmias).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo controlled
| Arm | Type | Receives |
|---|---|---|
| FlecIH-103 (flecainide acetate inhalation solution) | Active comparator | Drug: FlecIH-103Up to two 3.5-minute inhalations separated by a 1-minute break, for a total duration of up to 8 minutes on Day 1. Dosing will continue until conversion of AF to SR is observed for ≥1 minute or the full dose (120 mg eTLD) is administered, whichever occurs first. |
| Vehicle-matched inhalation solution (placebo) | Placebo comparator | Drug: FlecIH-103Up to two 3.5-minute inhalations separated by a 1-minute break, for a total duration of up to 8 minutes on Day 1. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- ≥18 and ≤85 years of age
- Recent onset of symptomatic newly diagnosed or paroxysmal AF
Key exclusion criteria (69 listed)
- History of non self-terminating AF/AFL as defined by
- Current diagnosis of persistent AF
- One or more episodes of AFL ≤6 months prior to randomization
- Hemodynamic or cardiac instability during AF, defined as any of the following:
- Respiratory rate >22 breaths per minute Relevant structural heart disease
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 |
|---|---|---|
| FlecIH-103flecainide acetate inhalation solution | Drug | FlecIH-103 (flecainide acetate inhalation solution), Vehicle-matched inhalation solution (placebo) |
Primary outcome
Assessment of proportion of patients whose AF converts using continuous ECG monitoring
Time frame: 90 minutes
To compare the efficacy of flecainide acetate inhalation solution and placebo for the conversion of atrial fibrillation (AF) to sinus rhythm (SR) in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Conversion from AF to SR will be monitored via continuous ECG recording. The efficacy of flecainide acetate solution and placebo will be compared using conversion as recorded on the ECG.
5 secondary outcomes
Time of conversion to be monitored using continuous ECGs
Time frame: 90 minutes
Assessing and comparing the AF related symptoms by using a questionnaire
Time frame: 90 minutes post dose
Assessing and comparing the hospital admissions between the active vs. placebo
Time frame: 90 minutes
Assessing and comparing the AF-related interventions prior to discharge between the active vs. placebo
Time frame: 90 minutes
Assessing and comparing the time of discharge
Time frame: 90 minutes
Results and safety
The study was stopped early (reason given: Limited efficacy upon blinded review). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
- Derived from this study: PubMed 40132102Rienstra M, Woite-Silva AC, Kuijper A, Eijsbouts S, Kraaier K, Janota T, Van Ofwegen C, Tuininga Y, Badings E, Merino JL, Ruskin JN, Camm AJ, Kowey PR, Dufton C, Maupas J, Parsell D, Belardinelli L. Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial. Europace. 2025 Mar 28;27(4):euaf064. doi: 10.1093/europace/euaf064.
- 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.
Luiz Belardinelli, MD study director
InCarda Therapeutics, Inc.
40 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FlecIH-103 in people with Paroxysmal Atrial Fibrillation, run by InCarda Therapeutics, Inc. at 40 sites in 6 countries.
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 6 inclusion and 69 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: stopped early, as of the sponsor's last update on 30 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Netherlands, Spain, Czechia, Hungary and 1 more country. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Limited efficacy upon blinded review). Results are not available in the source record.
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?
Assessment of proportion of patients whose AF converts using continuous ECG monitoring (time frame: 90 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05039359, which also lists 1 linked publication.
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 30 Oct 2023.