- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04676880
Left Atrial Appendage Occlusion for AF Patients Unable to Use Oral Anticoagulation Therapy (COMPARE-LAAO)
Comparing Effectiveness and Safety of Left Atrial Appendage Occlusion for Non-valvular Atrial Fibrillation Patients at High Stroke Risk Unable to Use Oral Anticoagulation Therapy
Study Overview
Status
Intervention / Treatment
Detailed Description
Stroke risk for non-valvular AF is estimated with the CHA2DS2-VASc score. When patients have no risk factors, no anticoagulation is recommended with a Class III, loe B. With 1 risk factor in men and 2 in women, anticoagulation should be considered (class IIA, loe-B). When the CHA2DS2-VASc score is 2 or greater in men (3 or greater in women) anticoagulation is recommended in all with a Class I, loe-A, preferably with a NOAC (class I, loe-A). Platelet inhibitor monotherapy is prohibited with a Class III, loe-A. Patients that have or develop a long-term contra-indication for oral anticoagulation have no class I guideline accepted alternative. Instead it is recommended to modify conditions or interrupt anticoagulants (Class IIB, loe-B). Resumption of oral anticoagulants should be guided by a multidisciplinary team that weighs the risks and benefits of such a course of action (class IIA, loe-C). In patients after an intracranial haemorrhage (ICH), it is recommended to initiate or resume anticoagulation after 2-4 weeks (class IIA, loeC) choosing an agent with low intracranial bleeding risk.
There is insufficient data to support the choice of anticoagulant and no evidence at all for avoiding stroke prevention altogether, which has led to wide variations in restarting oral anticoagulation often after several months of abstinence. Over 60% does not even resume therapy after anticoagulation-associated ICH.
As the LAA is the dominant source for cardioembolic stroke, mechanical percutaneous endocardial occlusion procedures have been developed. The WATCHMAN and AMULET (both FDA- and CE approval) are the most used but others are emerging. Basically, a cardiac catheterization is performed from the Femoral Vein, passing a 14F catheter through the Inferior Caval Vein and the interatrial septum to the left atrium. The delivery system is then positioned in the LAA ostium, and the device is deployed blocking the entrance and eliminating the LAA from the circulation. The implant procedure is usually guided by trans-esophageal echo imaging to assess device size and determine optimal position before it can be released. Adequate closure is achieved in 99% of patients nowadays, with a low and manageable procedural risk of 2.5%. To avoid device-related thrombus during reendothelialization patients are treated with dual antithrombotic agents, aspirin and clopidogrel in the first 3 months, which is narrowed down to aspirin until 1 year after which time it may be discontinued.
The 5-year follow up of PROTECT-AF and PREVAIL showed that LAAO was non-inferior to vitamin K antagonist (VKA) for the primary endpoint of stroke/ TIA/systemic embolism/death (HR 0.82, p-value 0.3), while VKA-patients had significantly more major bleeding events after the implant (HR 0.48, p=0.0003). WATCHMAN LAAO is CE and FDA approved and worldwide almost 100.000 WATCHMAN implantations have now been performed. Currently no RCT outcome data are available comparing WATCHMAN LAAO to any type of NOAC. For AMULET and other LAAO devices there are no published RCT compared to either VKA or NOAC. The EWOLUTION all-comers registry data in over 1000 AF pts (73% unable to use (N)OAC, CHA2DS2-VASc 4.7) WATCHMAN LAAO showed stroke and bleeding rates 80% and 46% lower than expected compared to historical data. In 2 similar AMPLATZER-AMULET LAAO registries of >1000 AF patients, stroke and bleeding rates were 50-60% lower. Both in the 2020 ESC and the 2019 AHA/ACC guidelines, LAAO has received a Class IIb, loe-B recommendation for stroke prevention in patients with AF that have non-reversible contra-indications for long-term anticoagulation.
The COMPARE-LAAO trial studies the effectiveness and safety of LAAO as an alternative means for stroke prevention, to establish whether outcomes in The Netherlands are comparable to literature. In the setting of a randomized controlled trial, LAA will be compared to usual care of anti-platelet therapy or nothing based on individual physician's assessment. Cost-effectiveness will be studied by comparing the additional cost of the procedure to cost of usual care, and the differences in cost between both arms for complications due to stroke and other embolism.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lucas VA Boersma, Prof. Dr.
- Phone Number: +31 (0)88 320 0900
- Email: l.boersma@antoniusziekenhuis.nl
Study Locations
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Groningen, Netherlands, 9713 GZ
- Active, not recruiting
- UMC Groningen
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Utrecht, Netherlands, 3584 CX
- Recruiting
- UMC Utrecht
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Contact:
- George Vlachojannis, MD, PhD
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Friesland
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Leeuwarden, Friesland, Netherlands, 8934 AD
- Active, not recruiting
- Medical Center Leeuwarden
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Gelderland
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Nijmegen, Gelderland, Netherlands, 6525 GA
- Not yet recruiting
- Radboud UMC
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Contact:
- Sjoerd Westra, MD
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Limburg
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Maastricht, Limburg, Netherlands, 6229 HX
- Not yet recruiting
- Maastricht UMC
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Contact:
- Marisevi Chaldoupi, MD, PhD
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Noord Holland
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Nieuwegein, Noord Holland, Netherlands, 3435 CM
- Recruiting
- St Antonius Hospital
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Contact:
- Lucas Boersma, prof. dr.
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Contact:
- Marina Huijboom
- Phone Number: +31 88 320 0900
- Email: m.huijboom@antoniusziekenhuis.nl
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Noord-Brabant
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Breda, Noord-Brabant, Netherlands, 4818 CK
- Not yet recruiting
- Amphia Hospital
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Contact:
- Sander IJsselmuiden, MD, PhD
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Noord-Holland
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Amsterdam, Noord-Holland, Netherlands, 1091 AC
- Not yet recruiting
- OLVG
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Contact:
- Muchtiar Khan, MD
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Amsterdam, Noord-Holland, Netherlands, 1105 AZ
- Not yet recruiting
- Amsterdam UMC
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Contact:
- Joris de Groot, MD, PhD
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Overijssel
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Enschede, Overijssel, Netherlands, 7512 KZ
- Not yet recruiting
- Medical Spectrum Twente
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Contact:
- Jeroen Stevenhagen, MD, PhD
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Zwolle, Overijssel, Netherlands, 8025 BT
- Not yet recruiting
- Isala Clinics
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Contact:
- Arif Elvan, MD, PhD
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Zuid Holland
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Den Haag, Zuid Holland, Netherlands, 2545 AA
- Not yet recruiting
- Haga Hospital
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Contact:
- Jeroen van der Heijden, MD, PhD
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Zuid-Holland
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Leiden, Zuid-Holland, Netherlands, 2333 ZA
- Not yet recruiting
- Leiden UMC
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Contact:
- Frank van der kley, MD
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Rotterdam, Zuid-Holland, Netherlands, 3015 GD
- Active, not recruiting
- Erasmus MC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Documented non-valvular AF (paroxysmal or non-paroxysmal) and
- CHA2DS2-VASc score of 2 or more and
- Unsuitable for long-term use of oral anticoagulation as determined by the referring physician team as well as the multidisciplinary team in the study hospital and
- Suitable for dual APT for at least 3 months and single APT from 3 until at most 12 months and
- At least 18 years of age, and willing and able to provide informed consent and adhere to study rules and regulations and follow-up
The decision of suitability for LAAO should be made by a multidisciplinary team consisting of at least an echocardiographist, an implanting cardiologist, and a cardiac surgeon. The decision of unsuitability for oral anticoagulation by the referring and implanting centers will be clearly and extensively documented in the study charts. This should include the support of physicians other than the referring and implanting cardiologist. These physicians should be specialists in the field where the contra-indication arises such as neurology, gastro-enterology, internal medicine, urology, or other specialties. In many cases the contra-indication may be due to (repeated) major bleeding.Bleeding will be classified according to the BARC criteria as major with a score of 3 or more. The risk of recurrent bleeding should be established by a multidisciplinary team, as well as the decision that the risk of bleeding recurrence outweighs the benefit of restarting oral anticoagulation, which will be documented in the charts. Alternative reasons not to use anticoagulation should be major and irreversible. These may be highly variable and may include but are not limited to occupational or life-style hazards, drug side-effects, ineffectiveness, intolerance, renal or liver failure, falling hazards, vascular problems, cerebral amyloid deposition, and coagulation disorders.
Exclusion Criteria:
- Any invasive cardiac procedure within 30 days prior to randomization and 90 days after LAAO that would interfere with the study follow-up and medication
- Unsuitable LAA anatomy for closure or thrombus in the LAA at the time of procedure
- Contraindications or unfavourable conditions to perform cardiac catheterization or TEE
- Atrial septal malformations, atrial septal defect or a high-risk patient foramen ovale that may cause thrombo-embolic events
- Atrial septal defect repair or closure device or a patent foramen ovale repair or any other anatomical condition as this may preclude an LAAO procedure
- LVEF<31% and/or heart failure NYHA 3-4
- Mitral valve regurgitation grade 3 or more
- Mitral stenosis as this makes AF by definition valvular in nature
- Aortic valve stenosis (AVA<1.0 cm2 or Pmax>50 mmHg) or regurgitation grade 3 or more
- Planned cardiac surgery for any reason within 3 months
- Stroke within the 3 months prior to inclusion, if not yet clinically stable, and/or without adequate diagnostic or prognostic evaluation, and/or in need of other interventions NL75209.100.20 COMPARE-LAAO Study protocol version 1.4 September 2020
- Planned CEA for significant carotid artery disease
- Major bleeding (BARC criteria>type 2) within 1 month prior to inclusion or longer if it has not been resolved yet
- Compelling medical reason to use VKA or NOAC (e.g. mechanical heart valve, pulmonary embolism, ventricular aneurysm)
- Major contraindications for using aspirin or clopidogrel
- (planned) pregnancy
- Participation in any other clinical trial that interferes with the current study
- Life expectancy of less than 1 year
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Intervention arm - Left atrial appendage occlusion (with Watchman FLX or Amplatzer Amulet device)
Patients randomized to the intervention arm will receive left atrial appendage occlusion.
In order to prevent device-related thrombus, they will use dual antiplatelet therapy (acetylsalicylzuur + clopidogrel) for three months and single antiplatelet therapy (acetylsalicylzuur) until at least 12 months after the procedure.
|
Currently, there are two devices available on the Dutch market, Watchman and Amulet.
After randomization to the intervention arm, additional randomization for type of device will follow.
If the amount of procedures is too small to implant two devices, the centre will implant a device of choice.
Other Names:
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No Intervention: Control arm - no or usual care
The patients in the control arm will stay on optimal treatment as decided by the referring physician (antiplatelet therapy or nothing).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to first occurrence of ischemic or hemorrhagic or undetermined stroke.
Time Frame: Minimal follow up is 1 year, maximum follow up +/- 5 years
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Minimal follow up is 1 year, maximum follow up +/- 5 years
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Time to first occurrence of the composite of stroke (ischemic or hemorrhagic or undetermined), TIA and systemic embolism.
Time Frame: Minimal follow up is 1 year, maximum follow up +/- 5 years
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Minimal follow up is 1 year, maximum follow up +/- 5 years
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Incidence of procedural complications
Time Frame: Procedure up to 30 days
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Defined as major procedure-related events that require prolonged hospitalization and/or specific treatment, or that lead to permanent physical or mental disability, including but not limited to: pericardiocentesis, major access site bleeding (BARC), any other major bleeding (BARC), device dislocation from the LAA to the heart or aorta, stroke, death, or other severe complications that are considered due to the procedure
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Procedure up to 30 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The composite event rate of stroke (ischemic or hemorrhagic), TIA, systemic embolism and cardiovascular death.
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Ischemic stroke event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Disabling stroke event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Hemorrhagic stroke event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
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TIA event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Systemic embolism (SE) event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Mortality (cardiovascular) event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Mortality (all-cause) event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
|
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Major bleeding event rate (according to BARC criteria)
Time Frame: both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
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both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
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Minor bleeding event rate
Time Frame: both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
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both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
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Number of patients with successful device deployment
Time Frame: procedural up to 7 days
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procedural up to 7 days
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Adverse events rate
Time Frame: at 30 days, and from 30 days until end of follow up (max. 5 years, avarage of 3 years)
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at 30 days, and from 30 days until end of follow up (max. 5 years, avarage of 3 years)
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Device related thrombus event rate
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
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Net-clinical benefit of efficacy and safety endpoint (calculated as the difference in time to first occurence of stroke, TIA and SE in both arms in comparison to the 30-day rate of procedural complications in both groups)
Time Frame: Through study completion, an average of 3 years
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Through study completion, an average of 3 years
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Patient-reported health quality assessed by the SF12 questionnaire
Time Frame: baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
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SF-12 stands for 12-Item Short Form Health Survey.
Every question is scored from 1 to 5 points.
Higher scores indicate better outcomes.
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baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
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Anxiety and depression assessed by the HADS questionnaire
Time Frame: baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
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HADS questionnaire stands for Hospital Anxiety and Depression Scale. The scale of the HADS-questionnaire lies between 0-21. For both anxiety and depression, de scores indicate:
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baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
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Generic health status assessed by the EQ5D5L questionnaire (in order to perform a cost-effectiveness analysis)
Time Frame: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
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EQ5D5L is a standardized instrument for measuring generic health status, widely used for (among other things) economic evaluations. The EQ5D5L consists of 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression), each with a scale/digit of 1-5 (where 1 indicates no problem and 5 indicates extreme problems). The digits for 5 dimensions can be combined in a 5-digit number describing a patients health state (this is no cardinal score). From these 5-digits numbers, a index value can be calculated. These index values will be compared between the different time frames and groups. |
Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
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Medical consumption (in order to perform a cost-effectiveness analysis)
Time Frame: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
|
iMCQ stands for iMTA Medical Consumption Questionnaire and is developed in order to improve standardization in measurement in health economic evaluation. The iMCQ is a generic instrument for measuring medical costs. The iMCQ includes questions related to frequently occurring contacts with health care providers. |
Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
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Productivity losses (in order to perform a cost-effectiveness analysis)
Time Frame: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
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iPCQ stands for iMTA Productivity Cost Questionnaire and is developed in order to improve standardization in measurement in health economic evaluation. The iPCQ is a generic questionnaire for the measurement of productivity losses. |
Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lucas VA Boersma, Prof. Dr., St Antonius Ziekenhuis Nieuwegein
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RDC-2020.01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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