A Trial of Cranberry Capsules for Urinary Tract Infection Prevention in Nursing Home Residents
Sponsor
Yale University (Other)
Overall Status
Completed
CT.gov ID
NCT01691430
Collaborator
National Institute on Aging (NIA) (NIH)
185
21
2
38
8.8
0.2
Study Details
Study Description
Brief Summary
Urinary tract infection (UTI) is the most common infection in nursing home residents, and bacteriuria is the greatest trigger for antimicrobial therapy in the nursing home setting. The primary aim of this study is to test the efficacy of two oral cranberry capsules per day in the reduction of bacteriuria plus pyuria in female nursing home residents. These aims will be accomplished by conducting a double blind randomized placebo controlled efficacy trial of two oral cranberry capsules daily versus placebo in a cohort of Connecticut female nursing home residents.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
185 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Participants were randomized to cranberry or placebo capsules.Participants were randomized to cranberry or placebo capsules.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Randomized, Controlled Trial of Cranberry Capsules for UTI Prevention in Nursing Home Residents
Study Start Date
:
Aug 1, 2012
Actual Primary Completion Date
:
Oct 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 2 cranberry capsules Experimental: 2 cranberry capsules |
Dietary Supplement: 2 cranberry capsules
Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC)
|
| Placebo Comparator: 2 placebo capsules Experimental: 2 placebo capsules qd |
Dietary Supplement: Placebo
Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC)
|
Outcome Measures
Primary Outcome Measures
- Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) [One year]
Clean catch urine cultures and urinalyses will be obtained every two months for each participant for study purposes.
Secondary Outcome Measures
- Number of Episodes of Symptomatic UTI [One year]
Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met.
- Number of Hospitalizations [One year]
- Number of Deaths [One year]
- Number of Antibiotic Prescriptions [One year]
Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant.
- Bacteriuria With Multidrug-resistant Gram-negative Bacilli [One year]
All urine culture data will be reviewed to determine presence of multidrug-resistant gram-negative bacilli (resistance to ≥3 of the following antibiotics: ampicillinsulbactam,cefazolin, ceftriaxone, ceftazidime, fluoroquinolones, piperacillin-tazobactam, meropenem, imipenem, and trimethoprim-sulfamethoxazole).
- Number of Antibiotic Prescriptions for Suspected UTI [One Year]
Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant's suspected UTI.
- Subjects With 1, 2, or 3 Episodes of UTIs [One year]
Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met.
Other Outcome Measures
- Number of Adverse Events in Participants [One year]
- Adherence to Capsule Intake by All Participants [One year]
measured by capsules removed from blister packs
Eligibility Criteria
Criteria
Ages Eligible for Study:
65 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
female residents;
-
long term residents
-
English speaking; and
-
age ≥ 65 years.
Exclusion Criteria:
-
residents that are not expected to be in the nursing home for at least one month (i.e., short term rehabilitation, pending discharge, terminal [life expectancy < 1 month]);
-
residents who are on chronic suppressive antibiotic or anti-infective (i.e., mandelamine) therapy for recurrent UTI;
-
residents with end stage renal disease on dialysis (they do not regularly produce urine);
-
residents unable to produce a baseline clean catch urine specimen for collection;
-
residents on warfarin therapy because of a potential interaction of warfarin and cranberry juice;
-
residents with a history of nephrolithiasis because cranberry may increase the risk of nephrolithiasis;
-
have an indwelling bladder catheter in place;
-
have an allergy to cranberry products;
-
are being treated with cranberry products;
-
residence <4 weeks.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Branford Hills Health Care | Branford | Connecticut | United States | 06405 |
| 2 | Northbridge Health Care Center | Bridgeport | Connecticut | United States | 06606 |
| 3 | Bridgeport Health Care Center | Bridgeport | Connecticut | United States | 06610 |
| 4 | Bridgeport Manor | Bridgeport | Connecticut | United States | 06610 |
| 5 | Riverside Health & Rehabilitation Center | East Hartford | Connecticut | United States | 06108 |
| 6 | Ludlowe Health Care Center | Fairfield | Connecticut | United States | 06825 |
| 7 | Glastonbury Health Care Center | Glastonbury | Connecticut | United States | 06033 |
| 8 | The Nathaniel Witherell | Greenwich | Connecticut | United States | 06830 |
| 9 | Arden House Care and Rehabilitation Center | Hamden | Connecticut | United States | 06514 |
| 10 | Hamden Health Care Center | Hamden | Connecticut | United States | 06514 |
| 11 | Avery Heights | Hartford | Connecticut | United States | 06106 |
| 12 | Wadsworth Glen Health Care and Rehabilitation Center | Middletown | Connecticut | United States | 06457 |
| 13 | Water's Edge Center for Health & Rehabilitation | Middletown | Connecticut | United States | 06457 |
| 14 | Grimes Center | New Haven | Connecticut | United States | 06511 |
| 15 | Mary Wade Home | New Haven | Connecticut | United States | 06511 |
| 16 | Advanced Nursing & Rehab Center of New Haven | New Haven | Connecticut | United States | 06519 |
| 17 | Shady Knoll Health Center | Seymour | Connecticut | United States | 06483 |
| 18 | Lord Chamberlain Nursing & Rehabilitation Center | Stratford | Connecticut | United States | 06614 |
| 19 | Village Green of Wallingford | Wallingford | Connecticut | United States | 06492 |
| 20 | Abbott Terrace Health Center | Waterbury | Connecticut | United States | 06702 |
| 21 | Hughes Health & Rehab Center | West Hartford | Connecticut | United States | 06119 |
Sponsors and Collaborators
- Yale University
- National Institute on Aging (NIA)
Investigators
- Principal Investigator: Manisha Juthani-Mehta, M.D., Yale School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Yale University
ClinicalTrials.gov Identifier:
NCT01691430
Other Study ID Numbers:
- 1112009472
- 2P30AG021342-11
- 1R01AG041153-01A1
First Posted:
Sep 24, 2012
Last Update Posted:
Mar 6, 2020
Last Verified:
Mar 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Recruited from nursing homes within 50 miles of New Haven. |
|---|---|
| Pre-assignment Detail | 806 patients were eligible, 558 declined to participate. Of the 248 consented, 63 were found to be ineligible after consent, leaving 185 to randomize. |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Period Title: Overall Study | ||
| STARTED | 92 | 93 |
| Received Medication | 92 | 93 |
| COMPLETED | 70 | 73 |
| NOT COMPLETED | 22 | 20 |
Baseline Characteristics
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules | Total |
|---|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Total of all reporting groups |
| Overall Participants | 92 | 93 | 185 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
92
100%
|
93
100%
|
185
100%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
92
100%
|
93
100%
|
185
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
83
90.2%
|
84
90.3%
|
167
90.3%
|
| Non-White |
9
9.8%
|
9
9.7%
|
18
9.7%
|
| Bacteriuria plus pyuria (participants) [Number] | |||
| Number [participants] |
27
29.3%
|
32
34.4%
|
59
31.9%
|
Outcome Measures
| Title | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) |
|---|---|
| Description | Clean catch urine cultures and urinalyses will be obtained every two months for each participant for study purposes. |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| 147 subjects completed 1 year, 33 died. 20 subjects, 9 in the treatment group v 11 in the control group, became incontinent prior to the first time point, thus unable to provide any urine. 45 subjects stopped taking the capsules, 24 in treatment and 21 in control; 21 refused, 19 transitioned to hospice, 4 started warfarin, and 1 refused via family. |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Baseline |
26
28.3%
|
32
34.4%
|
| 2 months |
21
22.8%
|
27
29%
|
| 4 months |
15
16.3%
|
26
28%
|
| 6 months |
13
14.1%
|
20
21.5%
|
| 8 months |
14
15.2%
|
14
15.1%
|
| 10 months |
15
16.3%
|
13
14%
|
| 12 months |
12
13%
|
9
9.7%
|
| Title | Number of Episodes of Symptomatic UTI |
|---|---|
| Description | Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met. |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [symptomatic urinary tract infections] |
10
|
12
|
| Title | Number of Hospitalizations |
|---|---|
| Description | |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [hospitilizations] |
33
|
50
|
| Title | Number of Deaths |
|---|---|
| Description | |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [participants] |
17
18.5%
|
16
17.2%
|
| Title | Number of Antibiotic Prescriptions |
|---|---|
| Description | Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant. |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [prescriptions] |
1415
|
1883
|
| Title | Bacteriuria With Multidrug-resistant Gram-negative Bacilli |
|---|---|
| Description | All urine culture data will be reviewed to determine presence of multidrug-resistant gram-negative bacilli (resistance to ≥3 of the following antibiotics: ampicillinsulbactam,cefazolin, ceftriaxone, ceftazidime, fluoroquinolones, piperacillin-tazobactam, meropenem, imipenem, and trimethoprim-sulfamethoxazole). |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [episodes] |
9
|
24
|
| Title | Number of Antibiotic Prescriptions for Suspected UTI |
|---|---|
| Description | Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant's suspected UTI. |
| Time Frame | One Year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [prescriptions] |
692
|
909
|
| Title | Number of Adverse Events in Participants |
|---|---|
| Description | |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Serious unrelated |
50
|
66
|
| non-serious unrelated |
1731
|
1966
|
| non-serious related |
7
|
7
|
| Title | Adherence to Capsule Intake by All Participants |
|---|---|
| Description | measured by capsules removed from blister packs |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| Number [percentage of capsules] |
77.5
|
82.6
|
| Title | Subjects With 1, 2, or 3 Episodes of UTIs |
|---|---|
| Description | Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met. |
| Time Frame | One year |
Outcome Measure Data
| Analysis Population Description |
|---|
| There were 10 symptomatic UTIs in the treatment group (8 participants with 1 episode and 1 participant with 2 episodes) and 12 symptomatic UTIs in the control group (7 participants with 1 episode, 1 participant with 2 episodes, and 1 participant with 3 episodes). |
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) |
| Measure Participants | 92 | 93 |
| 1 episode |
8
8.7%
|
7
7.5%
|
| 2 episodes |
1
1.1%
|
1
1.1%
|
| 3 episodes |
0
0%
|
1
1.1%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | 2 Cranberry Capsules | 2 Placebo Capsules | ||
| Arm/Group Description | Experimental: 2 cranberry capsules 2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | Experimental: 2 placebo capsules qd Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | ||
All Cause Mortality |
||||
| 2 Cranberry Capsules | 2 Placebo Capsules | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| 2 Cranberry Capsules | 2 Placebo Capsules | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 50/92 (54.3%) | 66/93 (71%) | ||
| General disorders | ||||
| Hospitalization | 33/92 (35.9%) | 50/93 (53.8%) | ||
| Death | 17/92 (18.5%) | 17 | 16/93 (17.2%) | 16 |
Other (Not Including Serious) Adverse Events |
||||
| 2 Cranberry Capsules | 2 Placebo Capsules | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 92/92 (100%) | 93/93 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Abnormal blood glucose | 9/92 (9.8%) | 11/93 (11.8%) | ||
| Anemia | 4/92 (4.3%) | 4/93 (4.3%) | ||
| Blood pressure alteration | 14/92 (15.2%) | 14/93 (15.1%) | ||
| Ear and labyrinth disorders | ||||
| ear problem | 6/92 (6.5%) | 11/93 (11.8%) | ||
| Eye disorders | ||||
| eye infection | 18/92 (19.6%) | 17/93 (18.3%) | ||
| Gastrointestinal disorders | ||||
| constipation | 47/92 (51.1%) | 51/93 (54.8%) | ||
| GI disturbance | 53/92 (57.6%) | 53/93 (57%) | ||
| General disorders | ||||
| Back Pain | 11/92 (12%) | 17/93 (18.3%) | ||
| dehydration | 1/92 (1.1%) | 1/93 (1.1%) | ||
| edema | 17/92 (18.5%) | 21/93 (22.6%) | ||
| Fall | 48/92 (52.2%) | 55/93 (59.1%) | ||
| fever | 18/92 (19.6%) | 21/93 (22.6%) | ||
| Generalized malaise | 29/92 (31.5%) | 27/93 (29%) | ||
| headache | 10/92 (10.9%) | 19/93 (20.4%) | ||
| insomnia | 6/92 (6.5%) | 10/93 (10.8%) | ||
| joint pain | 36/92 (39.1%) | 31/93 (33.3%) | ||
| lab abnormality | 42/92 (45.7%) | 43/93 (46.2%) | ||
| oral cavity disturbance | 34/92 (37%) | 25/93 (26.9%) | ||
| Infections and infestations | ||||
| exposure to influenza | 10/92 (10.9%) | 13/93 (14%) | ||
| Metabolism and nutrition disorders | ||||
| weight gain | 42/92 (45.7%) | 48/93 (51.6%) | ||
| weight loss | 62/92 (67.4%) | 74/93 (79.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| leg pain | 8/92 (8.7%) | 9/93 (9.7%) | ||
| Nervous system disorders | ||||
| dizziness | 4/92 (4.3%) | 6/93 (6.5%) | ||
| Psychiatric disorders | ||||
| Altered mental status | 53/92 (57.6%) | 61/93 (65.6%) | ||
| Renal and urinary disorders | ||||
| Acute renal failure | 1/92 (1.1%) | 0/93 (0%) | ||
| Urinary Tract Infection | 33/92 (35.9%) | 44/93 (47.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute chest pain | 9/92 (9.8%) | 11/93 (11.8%) | ||
| respiratory difficulty | 55/92 (59.8%) | 59/93 (63.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| skin/soft tissue event | 71/92 (77.2%) | 83/93 (89.2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Manisha Juthani-Mehta |
|---|---|
| Organization | Yale University |
| Phone | (203)785-4140 |
| manisha.juthani@yale.edu |
Responsible Party:
Yale University
ClinicalTrials.gov Identifier:
NCT01691430
Other Study ID Numbers:
- 1112009472
- 2P30AG021342-11
- 1R01AG041153-01A1
First Posted:
Sep 24, 2012
Last Update Posted:
Mar 6, 2020
Last Verified:
Mar 1, 2020