Myocardial IschemiaPhase 3PERFECTNCT00950274
Intramyocardial Transplantation of Bone Marrow Stem Cells in Addition to Coronary Artery Bypass Graft (CABG) Surgery
A Phase 3 study testing CD133+ autologous bone marrow stem cell in people with Myocardial Ischemia and Coronary Artery Disease, run by Miltenyi Biotec B.V. & Co. KG at 6 sites in Germany.
Trial summary
In spite of the fact that the post-myocardial infarction survival rate has improved with recent medical advances, reduced heart function attributed to irreversible loss of viable cardiomyocytes is still a major clinical problem. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Myocardial Ischemia, Coronary Artery Disease
- What is being tested?
- CD133+ autologous bone marrow stem cell
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 6 sitesGermany
- Study dates
- Jul 2009to Sep 2017
- 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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Coronary artery disease after myocardial infarction with indication for CABG surgery
- Currently reduced global LVEF assessed at site by cardiac MRI at rest (25% ≤ LVEF ≤ 50%)
- Presence of a localized akinetic/hypokinetic/hypoperfused area of LV myocardium for defining the target area
- Informed consent of the patient
- 18 years ≤ Age < 80 years
- Are not pregnant and do not plan to become pregnant during the study. Females with childbearing potential must provide a negative pregnancy test within 1-7 days before OP and must be using oral or injectable contraception (non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start).
Who cannot join
- Emergency operation
- Presence of any moderate-severe valvular heart disease requiring concomitant valve replacement or reconstruction
- Medical History of recent resuscitation in combination with ventricular arrhythmia classified by LOWN ≥ class II
- Acute myocardial infarction within last 2 weeks
- Debilitating other disease: Degenerative neurologic disorders, psychiatric disease, terminal renal failure requiring dialysis, previous organ transplantation, active malignant neoplasia, or any other serious medical condition that, in the opinion of the Investigator is likely to alter the patient's course of recovery or the evaluation of the study medication's safety
- Impaired ability to comprehend the study information
Show all 17Show fewer
- Absent informed written consent
- Treatment with any investigational drug within the previous 30 days
- Apparent infection (c-reactive protein [CRP] ≥ 20 mg/L, fever ≥ 38.5° C)
- Contraindication for MRI scan
- Immune compromise including active infection with Hepatitis B, C, HIV virus or seropositivity for Treponema pallidum
- Pregnant or breast feeding
- Childbearing potential with unreliable birth control methods
- Have previously been enrolled in this study, respectively phase I and phase II
- Known hypersensitivity or sensitization against murine products and human-anti-mouse-antibody-titer ≥ 1:1000
- Contraindication to bone marrow aspiration
- Known hypersensitivity against iron dextran
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Herz- und Diabeteszentrum Nordrhein Westfalen
Bad Oeynhausen, 32545
Deutsches Herzzentrum Berlin
Berlin, 13353
Universitäres Herzzentrum Hamburg
Hamburg, 20246
Medical School Hannover
Hanover, 30625
Herzzentrum Universität Leipzig
Leipzig, 04289
University of Rostock
Rostock, 18057
About this study
Official title: Intramyocardial Transplantation of Bone Marrow Stem Cells for Improvement of Post-infarct Myocardial Regeneration in Addition to CABG Surgery: a Controlled, Prospective, Randomized, Double Blinded Multicenter Trial (PERFECT)
In spite of the fact that the post-myocardial infarction survival rate has improved with recent medical advances, reduced heart function attributed to irreversible loss of viable cardiomyocytes is still a major clinical problem.
The aim of the current study is to determine whether intramyocardial injection of autologous CD133+ bone marrow stem cells yields a functional benefit in addition to coronary artery bypass graft (CABG) surgery in patients with chronic ischemic coronary artery disease.
Read the detailed description
Beginning in 2001, a phase-1 equivalent feasibility and safety evaluation of intramyocardial injection of autologous CD133+ bone marrow cells during elective CABG surgery was conducted at Rostock University. No procedure-related adverse events were observed and there was some improvement of myocardial contractility and perfusion. It was decided to proceed with a controlled efficacy testing, comparing the outcome of standard CABG surgery with that after CABG and CD133+ cell injection. The results of that study indicate that the additional cell injection yields a better left ventricular contractility than CABG alone (LVEF = 47.1±8% vs. 41.3±9% at 6 months). Although this result is encouraging, the trial had several limitations that hamper interpretation of the data. Most notably, no sham-injection of placebo material was performed in the control group, and standard 2D echocardiography served as the only measurement of global LV contractility.
However, there were no procedure-related complications up to 18 months postoperatively, especially no new ventricular arrhythmia or neoplasia.
Therefore, a prospective, double blinded, randomized, and placebo-controlled multi-center trial will be conducted in Germany, employing current state-of-the art measurement of global and regional LV contractility by cardiac MRI. The following hypothesis will be tested: "Patients who undergo CABG \& CD133+ cell injection do not have a higher LV ejection fraction than patient who undergo CABG alone, measured 6 months after the operation". A power analysis based on the previous trial results indicated that 71 patients per group need to be enrolled so as to reject the null-hypothesis with sufficient statistical power. A total of 142 patients will therefore be enrolled in the study. Patients will be randomized in a 1:1 ratio to undergo CABG surgery in conjunction with either intramyocardial injection of autologous CD133-enriched bone marrow cells or placebo. Bone marrow will be harvested one or two days prior to surgery and a CD133-enriched cell product (or placebo) will be prepared at a central cell processing GMP unit. Bypass surgery will be performed and the investigational product will be injected in the border zone of the infarcted myocardium. Random allocation will be performed in the cell production facility, so that neither the patient nor the surgeon nor any of the personnel involved in follow-up examinations will know whether the cell product or placebo was administered. The primary outcome parameter (LVEF at 6 months) will be measured by cardiac MRI, and secondary outcome parameters include physical exercise capacity, cardiac function, safety and Quality of Life (QoL).
- Conditions
- Myocardial Ischemia, Coronary Artery Disease
- Being tested
- CD133+ autologous bone marrow stem cell, Placebo
- Keywords
- Cell therapy, Bone marrow, CD133, Bypass surgery, Stem cells, Myocardial infarction, Myocardial ischemia
- Medical subject headings
- Myocardial Ischemia, Coronary Artery Disease, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD133+ autologous bone marrow stem cellDrug
Intramyocardial injection of 5 mL CD133+ cells (0.5-5x10e6 cells) suspended in physiological saline + 10% autologous serum intramyocardially during CABG surgery
PlaceboDrug
Intramyocardial injection of 5 mL of physiological saline + 10% autologous serum intramyocardially during CABG surgery
| Study group | Role | What they receive |
|---|---|---|
| CD133+ autologous bone marrow stem cells | Active comparator | Not described Receives: Drug: CD133+ autologous bone marrow stem cell |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular ejection fraction at rest, measured by MRI
Measured: 6 months
Secondary outcomes (6)
Change in LVEF as assessed by MRI and echocardiography
Measured: early postoperatively and 6 months
Regional contractility in the AOI / Change in LV dimensions (left ventricular end systolic diameter [LVESD], left ventricular end diastolic diameter [LVEDD]) as assessed by echocardiography
Measured: early postoperatively (discharge), 6 months
Physical exercise capacity determined by 6 minute walk test
Measured: early postoperatively (discharge), 6 months
NYHA and CCS class
Measured: early postoperatively (discharge), 6 months
MACE (cardiac death, myocardial infarction, secondary intervention/reoperation, ventricular arrhythmia)
Measured: 6 months
QoL-score: Minnesota Living with Heart Failure Questionnaire, SF36 Questionnaire, EQ-5D Questionnaire
Measured: 3 months, 6 months post-OP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionMar 2016
- Study completionSep 2017
Why it stopped: Recruitment stopped due to slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myocardial IschemiaStudies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Miltenyi Biotec B.V. & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- German Federal Ministry of Education and Research
- Responsible party
- Sponsor
- Investigators
- Gustav Steinhoff, M.D., Principal investigator, Universitiy of Rostock
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00950274
- Sponsor's protocol ID
- PERFECT 001
- Other IDs
- M-2006-144
- Acronym
- PERFECT
- Status last verified
- Aug 2018
- First submitted
- 30 Jul 2009
- Last updated
- 15 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wolfien M, Klatt D, Salybekov AA, Ii M, Komatsu-Horii M, Gaebel R, Philippou-Massier J, Schrinner E, Akimaru H, Akimaru E, David R, Garbade J, Gummert J, Haverich A, Hennig H, Iwasaki H, Kaminski A, Kawamoto A, Klopsch C, Kowallick JT, Krebs S, Nesteruk J, Reichenspurner H, Ritter C, Stamm C, Tani-Yokoyama A, Blum H, Wolkenhauer O, Schambach A, Asahara T, Steinhoff G. Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3. EBioMedicine. 2020 Jul;57:102862. doi: 10.1016/j.ebiom.2020.102862. Epub 2020 Jul 4.
PubMed 32629392Steinhoff G, Nesteruk J, Wolfien M, Kundt G; PERFECT Trial Investigators Group; Borgermann J, David R, Garbade J, Grosse J, Haverich A, Hennig H, Kaminski A, Lotz J, Mohr FW, Muller P, Oostendorp R, Ruch U, Sarikouch S, Skorska A, Stamm C, Tiedemann G, Wagner FM, Wolkenhauer O. Cardiac Function Improvement and Bone Marrow Response -: Outcome Analysis of the Randomized PERFECT Phase III Clinical Trial of Intramyocardial CD133+ Application After Myocardial Infarction. EBioMedicine. 2017 Aug;22:208-224. doi: 10.1016/j.ebiom.2017.07.022. Epub 2017 Jul 29.
PubMed 28781130Donndorf P, Kaminski A, Tiedemann G, Kundt G, Steinhoff G. Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial. Trials. 2012 Jul 2;13:99. doi: 10.1186/1745-6215-13-99.
PubMed 22747980
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intramyocardial Transplantation of Bone Marrow Stem Cells for Improvement of Post-infarct Myocardial Regeneration in Addition to CABG Surgery: a Controlled, Prospective, Randomized, Double Blinded Multicenter Trial (PERFECT)
- ClinicalTrials.gov ID
- NCT00950274
- Acronym / sponsor ID
- PERFECT / PERFECT 001
- Conditions
- Myocardial Ischemia, Coronary Artery Disease
- Keywords
- Cell therapy, Bone marrow, CD133, Bypass surgery, Stem cells, Myocardial infarction, Myocardial ischemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment stopped due to slow recruitment
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Miltenyi Biotec B.V. & Co. KGIndustry (pharma, biotech, devices)
- Collaborators
- German Federal Ministry of Education and Research
- Study start
- Jul 2009
- Primary completion
- Mar 2016 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 31 Jul 2009 (estimated)
- 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.
In spite of the fact that the post-myocardial infarction survival rate has improved with recent medical advances, reduced heart function attributed to irreversible loss of viable cardiomyocytes is still a major clinical problem.
The aim of the current study is to determine whether intramyocardial injection of autologous CD133+ bone marrow stem cells yields a functional benefit in addition to coronary artery bypass graft (CABG) surgery in patients with chronic ischemic coronary artery disease.
Detailed description
Beginning in 2001, a phase-1 equivalent feasibility and safety evaluation of intramyocardial injection of autologous CD133+ bone marrow cells during elective CABG surgery was conducted at Rostock University. No procedure-related adverse events were observed and there was some improvement of myocardial contractility and perfusion. It was decided to proceed with a controlled efficacy testing, comparing the outcome of standard CABG surgery with that after CABG and CD133+ cell injection. The results of that study indicate that the additional cell injection yields a better left ventricular contractility than CABG alone (LVEF = 47.1±8% vs. 41.3±9% at 6 months). Although this result is encouraging, the trial had several limitations that hamper interpretation of the data. Most notably, no sham-injection of placebo material was performed in the control group, and standard 2D echocardiography served as the only measurement of global LV contractility.
However, there were no procedure-related complications up to 18 months postoperatively, especially no new ventricular arrhythmia or neoplasia.
Therefore, a prospective, double blinded, randomized, and placebo-controlled multi-center trial will be conducted in Germany, employing current state-of-the art measurement of global and regional LV contractility by cardiac MRI. The following hypothesis will be tested: "Patients who undergo CABG \& CD133+ cell injection do not have a higher LV ejection fraction than patient who undergo CABG alone, measured 6 months after the operation". A power analysis based on the previous trial results indicated that 71 patients per group need to be enrolled so as to reject the null-hypothesis with sufficient statistical power. A total of 142 patients will therefore be enrolled in the study. Patients will be randomized in a 1:1 ratio to undergo CABG surgery in conjunction with either intramyocardial injection of autologous CD133-enriched bone marrow cells or placebo. Bone marrow will be harvested one or two days prior to surgery and a CD133-enriched cell product (or placebo) will be prepared at a central cell processing GMP unit. Bypass surgery will be performed and the investigational product will be injected in the border zone of the infarcted myocardium. Random allocation will be performed in the cell production facility, so that neither the patient nor the surgeon nor any of the personnel involved in follow-up examinations will know whether the cell product or placebo was administered. The primary outcome parameter (LVEF at 6 months) will be measured by cardiac MRI, and secondary outcome parameters include physical exercise capacity, cardiac function, safety and Quality of Life (QoL).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD133+ autologous bone marrow stem cells | Active comparator | Drug: CD133+ autologous bone marrow stem cell |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Coronary artery disease after myocardial infarction with indication for CABG surgery
- Currently reduced global LVEF assessed at site by cardiac MRI at rest (25% ≤ LVEF ≤ 50%)
- Presence of a localized akinetic/hypokinetic/hypoperfused area of LV myocardium for defining the target area
- Informed consent of the patient
- 18 years ≤ Age < 80 years
Key exclusion criteria (17 listed)
- Emergency operation
- Presence of any moderate-severe valvular heart disease requiring concomitant valve replacement or reconstruction
- Medical History of recent resuscitation in combination with ventricular arrhythmia classified by LOWN ≥ class II
- Acute myocardial infarction within last 2 weeks
- Debilitating other disease: Degenerative neurologic disorders, psychiatric disease, terminal renal failure requiring dialysis, previous organ transplantation, active malignant neoplasia, or any other serious medical condition that, in the opinion of the Investigator is likely to alter the patient's course of recovery or the evaluation of the study medication's safety
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 |
|---|---|---|
| CD133+ autologous bone marrow stem cellIntramyocardial injection of 5 mL CD133+ cells (0.5-5x10e6 cells) suspended in physiological saline + 10% autologous serum intramyocardially during CABG surgery | Drug | CD133+ autologous bone marrow stem cells |
| PlaceboIntramyocardial injection of 5 mL of physiological saline + 10% autologous serum intramyocardially during CABG surgery | Drug | Placebo |
Primary outcome
Left ventricular ejection fraction at rest, measured by MRI
Time frame: 6 months
6 secondary outcomes
Change in LVEF as assessed by MRI and echocardiography
Time frame: early postoperatively and 6 months
Regional contractility in the AOI / Change in LV dimensions (left ventricular end systolic diameter [LVESD], left ventricular end diastolic diameter [LVEDD]) as assessed by echocardiography
Time frame: early postoperatively (discharge), 6 months
Physical exercise capacity determined by 6 minute walk test
Time frame: early postoperatively (discharge), 6 months
NYHA and CCS class
Time frame: early postoperatively (discharge), 6 months
MACE (cardiac death, myocardial infarction, secondary intervention/reoperation, ventricular arrhythmia)
Time frame: 6 months
QoL-score: Minnesota Living with Heart Failure Questionnaire, SF36 Questionnaire, EQ-5D Questionnaire
Time frame: 3 months, 6 months post-OP
Results and safety
The study was stopped early (reason given: Recruitment stopped due to slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
- Derived from this study: PubMed 32629392Wolfien M, Klatt D, Salybekov AA, Ii M, Komatsu-Horii M, Gaebel R, Philippou-Massier J, Schrinner E, Akimaru H, Akimaru E, David R, Garbade J, Gummert J, Haverich A, Hennig H, Iwasaki H, Kaminski A, Kawamoto A, Klopsch C, Kowallick JT, Krebs S, Nesteruk J, Reichenspurner H, Ritter C, Stamm C, Tani-Yokoyama A, Blum H, Wolkenhauer O, Schambach A, Asahara T, Steinhoff G. Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3. EBioMedicine. 2020 Jul;57:102862. doi: 10.1016/j.ebiom.2020.102862. Epub 2020 Jul 4.
- Derived from this study: PubMed 28781130Steinhoff G, Nesteruk J, Wolfien M, Kundt G; PERFECT Trial Investigators Group; Borgermann J, David R, Garbade J, Grosse J, Haverich A, Hennig H, Kaminski A, Lotz J, Mohr FW, Muller P, Oostendorp R, Ruch U, Sarikouch S, Skorska A, Stamm C, Tiedemann G, Wagner FM, Wolkenhauer O. Cardiac Function Improvement and Bone Marrow Response -: Outcome Analysis of the Randomized PERFECT Phase III Clinical Trial of Intramyocardial CD133+ Application After Myocardial Infarction. EBioMedicine. 2017 Aug;22:208-224. doi: 10.1016/j.ebiom.2017.07.022. Epub 2017 Jul 29.
- Derived from this study: PubMed 22747980Donndorf P, Kaminski A, Tiedemann G, Kundt G, Steinhoff G. Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial. Trials. 2012 Jul 2;13:99. doi: 10.1186/1745-6215-13-99.
Related trials for Myocardial Ischemia
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
RecruitingEarly Phase 1
Thiamine Intervention and Coronary Artery Bypass Grafting
Coronary Heart Disease, Coronary Artery Bypass Grafting
Active, not recruitingObservational study
A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti
Hypertension, Diabetes
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.
Gustav Steinhoff, M.D. principal investigator
Universitiy of Rostock
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CD133+ autologous bone marrow stem cell in people with Myocardial Ischemia and Coronary Artery Disease, run by Miltenyi Biotec B.V. & Co. KG at 6 sites in Germany.
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 17 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 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. 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: Recruitment stopped due to slow recruitment). 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?
Left ventricular ejection fraction at rest, measured by MRI (time frame: 6 months). 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 NCT00950274, which also lists 3 linked publications.
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 15 Jul 2020.