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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03948178
Registration number
NCT03948178
Ethics application status
Date submitted
7/05/2019
Date registered
13/05/2019
Date last updated
9/03/2023
Titles & IDs
Public title
Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
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Scientific title
Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS: Open-Label Extension for Patients Completing Study 3119002
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Secondary ID [1]
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3119003
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Universal Trial Number (UTN)
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Trial acronym
REFALS-ES
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis
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Condition category
Condition code
Neurological
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Neurodegenerative diseases
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Levosimendan
Experimental: Levosimendan - Oral Levosimendan; Levosimendan 1mg capsules for oral administration, once to twice a day, continued as long as clinically beneficial. The total study duration is up to 3 years.
Treatment: Drugs: Levosimendan
Levosimendan 1 mg capsule for oral administration
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Adverse Events Recording
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Assessment method [1]
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Adverse Events as subject counts and proportions (%) of subject per Adverse Event
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Timepoint [1]
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From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.
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Primary outcome [2]
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Pulse/Heart Rate Assessment
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Assessment method [2]
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Actual values and changes from baseline in supine pre-dose pulse/heart rate were summarised using descriptive statistics .
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Timepoint [2]
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Change in pulse and heart rate(from ECG recording) from Baseline, week 2, week 4, week 6 (pulse rate only), Month 3, Month 6, end of study (subject's last visit, 2-48 weeks after study entry)
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Primary outcome [3]
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12-lead Electrocardiogram Assessments
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Assessment method [3]
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Summarisation of any abnormal 12-lead ECG findings using descriptive statistics.
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Timepoint [3]
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Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry)
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Secondary outcome [1]
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Disease Progression
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Assessment method [1]
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Count of study withdrawals due to disease progression
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Timepoint [1]
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From Baseline through study completion(subject's last visit, 2-48 weeks after study entry)
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Secondary outcome [2]
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Supine Slow Vital Capacity (SVC)
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Assessment method [2]
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Change from baseline in supine and sitting SVC (all devices) through to the end of the study, expressed as a % of predicted normal
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Timepoint [2]
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The change from Baseline, week 2, week 4, month 3, month 6, end-of-study (subject's last visit, 2-48 weeks after study entry)
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Secondary outcome [3]
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Revised ALS Functional Rating Scale (ALSFRS-R)
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Assessment method [3]
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ALSFRS-R scale contains 3 parameters related to respiratory function: Severity of dyspnea, occurrence of orthopnea (shortness of breath when in supine position i.e. lying flat), and the use of mechanical ventilation for respiratory in sufficiency. These 3 parameters are combined to create the respiratory domain with a score of 0-12(where 12 is normal function). Although individual items and patients vary, ALSFRS-R typically declines at a relatively constant rate over time. Plotted over time the slope of the line obtained indicates the speed of progression and thus an effective treatment might be expected ro reduce the slope of decline.
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Timepoint [3]
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Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry)
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Secondary outcome [4]
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Need for Respiratory Support Device
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Assessment method [4]
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Time to respiratory device support (non invasive) or death
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Timepoint [4]
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Time to event at study completion (subject's last visit, 2-48 weeks after study entry)
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Secondary outcome [5]
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Borg Category Ratio 10 Scale (CR 10)
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Assessment method [5]
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Patients rated their perception of the severity of their dyspnea using the Borg Category Ration 10 scale (CR 10). The scale ranges from 0(no dysponea) to 10 (maximal dyspnea). each category is numbered and most but not all have verbal cues. At each assessment the patient scored the category they felt best described their symptoms. The analysis measured change from baseline to the end of the study in both a supine and sitting position where a negative score indicates improvement and a positive score reflects worsening.
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Timepoint [5]
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Baseline through study completion (week 2, week 4, month 3, month 6, end of study (subject's last visit, 2-48 weeks after study entry)
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Secondary outcome [6]
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Number of Subjects Requiring Health and Home Care Resource Use
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Assessment method [6]
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The number of study subjects requiring Health and home care resource use was aggregated over the course of the study for each subject and summarised using descriptive statistics.
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Timepoint [6]
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Baseline through study completion (2- 48 weeks after study entry)
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Secondary outcome [7]
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Subject's Status for Tracheostomy and Survival
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Assessment method [7]
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Number of patients with the need for tracheostomy or who died whilst on treatment from baseline to the end of the study was summarised using descriptive statistics.
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Timepoint [7]
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Baseline to end of study (average 2-48 weeks after study entry
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Secondary outcome [8]
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Health Care Service Use During the Study(Stays in Hospital)
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Assessment method [8]
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The number of night stays in hospital were recorded throughout the study using a diary given to the study subjects
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Timepoint [8]
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From baseline to the end of the study(2-48 weeks after study entry)
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Secondary outcome [9]
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Health Care Service Use During the Study(Visits to the Emergency Room)
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Assessment method [9]
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The number of visits to the emergency room were recorded throughout the study using a diary given to the study subjects
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Timepoint [9]
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From baseline to the end of the study(2-48 weeks after study entry)
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Secondary outcome [10]
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Health Care Service Use During the Study (Days Spent in an Institutional Facility)
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Assessment method [10]
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The number of days spent in an institutional facility were recorded throughout the study using a diary given to the study subjects
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Timepoint [10]
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From baseline to the end of the study(2-48 weeks after study entry)
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Eligibility
Key inclusion criteria
* Written or verbal informed consent (IC) for participation in the study
* Subjects who completed 48 weeks of treatment according to the REFALS study protocol
* Able to swallow study treatment capsules at the time of completing 48 weeks dosing in the REFALS study
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Minimum age
18
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Maximum age
120
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Development (or significant worsening from baseline of the REFALS study) of serious cardiovascular disease (e.g.: myocardial infarction, heart failure, arrhythmia, stroke, or second or third degree atrioventricular (AV) block)
* Pulse/heart rate repeatedly >100 bpm after 5-minute rest at baseline. If the pulse/heart rate is >100 bpm in the first recording, then a second recording must be done after another 5 min rest to confirm pulse/heart rate >100 bpm
* Systolic blood pressure (SBP) <90 mmHg
* Severe renal impairment (creatinine clearance < 30ml/min or creatine >170 µmol/l at 48 week visit of the REFALS study, or on dialysis
* Severe hepatic impairment at the discretion of the investigator
* Women of reproductive age without a negative pregnancy test and without a commitment to using a highly effective method of contraception (e.g.: oral hormonal contraceptive associated with inhibition of ovulation, intrauterine devices and long acting progestin agent), if sexually active during the study, and for 1 month after the last dose of the study treatment. Women who are postmenopausal (1 year since last menstrual cycle), surgically sterilised or who have undergone a hysterectomy are considered not to be reproductive and can be included
* Subject judged to be actively suicidal by the investigator
* Any other clinical significant cardiovascular, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator could interfere with the interpretation of the study results or constitute a health risk for the subject if he/she took part in the study
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Study design
Purpose of the study
Treatment
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Allocation to intervention
NA
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/06/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
18/11/2020
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Sample size
Target
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Accrual to date
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Final
227
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Brain and Mind Centre - Camperdown
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Recruitment hospital [2]
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Royal Brisbane and Women's Hospital - Herston
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Recruitment hospital [3]
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Flinders Medical Centre - Bedford Park
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Recruitment hospital [4]
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Calvary Health Care Bethlehem - Parkdale
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Recruitment hospital [5]
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Perron Institute for Neurological and Translational Science - Nedlands
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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4029 - Herston
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5042 - Bedford Park
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Recruitment postcode(s) [4]
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3195 - Parkdale
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Recruitment postcode(s) [5]
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6009 - Nedlands
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Recruitment outside Australia
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Connecticut
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Orion Corporation, Orion Pharma
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This study provides an opportunity for subjects in the REFALS (3119002; NCT03505021) study to continue treatment with oral levosimendan. The study will also provide more information about long-term safety and effectiveness of oral levosimendan in patients with ALS. This is an open-label study, so that all eligible subjects that complete the double-blind REFALS study (48-weeks of treatment) will have the opportunity to receive oral levosimendan treatment. The primary objective, in addition to continuing treatment for subjects enrolled in the REFALS study, is to evaluate long-term safety of oral levosimendan in ALS patients. Another important objective is to explore long-term effectiveness of oral levosimendan in the treatment of patients with ALS. This study is open only to patients taking part in the REFALS study.
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Trial website
https://clinicaltrials.gov/study/NCT03948178
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Trial related presentations / publications
Cudkowicz M, Genge A, Maragakis N, Petri S, van den Berg L, Aho VV, Sarapohja T, Kuoppamaki M, Garratt C, Al-Chalabi A; REFALS investigators. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2021 Oct;20(10):821-831. doi: 10.1016/S1474-4422(21)00242-8.
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Public notes
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Contacts
Principal investigator
Name
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Geneviève Nadeau, CSD
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Address
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Orion Corporation, Orion Pharma
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/78/NCT03948178/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/78/NCT03948178/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03948178
Download to PDF