Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure (DIAMOND)
- Registration Number
- NCT03888066
- Lead Sponsor
- Vifor Pharma, Inc.
- Brief Summary
The purpose of this study is to assess the effects of patiromer compared with placebo on serum K+ in HF patients.
- Detailed Description
Prospective Phase 3b multinational, multicenter, double-blind, placebo-controlled, randomized withdrawal, parallel group study that includes screening and up to 12 weeks Run-in Phase (all subjects will have patiromer initiated and RAASi medications, including mineralocorticoid receptor antagonist (MRA) optimized) and a randomized withdrawal Blinded Treatment Phase.
The study population includes subjects with heart failure (HF) with reduced ejection fraction (HFrEF) who are hyperkalemic (serum potassium \[K+\] \> 5.0 mEq/L) while receiving treatment with renin angiotensin aldosterone system inhibitor (RAASi) medications or who are normokalemic (serum K+ 4.0 - 5.0 mEq/L) but have a history of hyperkalemia prior to screening with subsequent reduction or discontinuation of a RAASi medication.
Each subject's participation includes a Run-in Phase (maximum 12 weeks) followed by the Treatment Phase (variable per subject). Study duration for individual subjects will vary, depending on their individual enrollment date. Subjects who prematurely discontinue patiromer/placebo will remain in the study for the collection of clinical events data and will receive usual care.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1195
- Age at least 18 years or greater
- Symptomatic low ejection fraction heart failure (weak heart muscle)
- Receiving any dose of a beta blocker for the treatment of HF (unless not able to tolerate)
- Kidney function not more than mild or moderately impaired
- High blood potassium (>5.0 mEq/L) currently while receiving medications for heart failure OR normal blood potassium currently but previously had high potassium in the12 months prior to screening which caused a permanent reduction or discontinuation of heart failure medications
- Hospitalization for heart failure or treatment in an out patient setting with intravenous medications within the last 12 months before screening.
- Current acute decompensated HF, within 4 weeks before screening. Subjects with a discharge from a hospitalization for acute decompensation of HF longer than 4 weeks before screening may be included
- Significant primary aortic or mitral valvular heart disease (except secondary mitral regurgitation due to left ventricular dilatation)
- Heart transplantation or planned heart transplantation (i.e., currently on a heart transplant waiting list) during the study period
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: Placebo Placebos Subjects will be randomized to receive a daily dose of placebo with possible dose adjustments based on subsequent local serum potassium levels. Group 1: Patiromer Patiromer Subjects will be randomized to receive a daily dose of patiromer with possible dose adjustments based on subsequent local serum potassium levels.
- Primary Outcome Measures
Name Time Method Changes in Serum K+ Levels From Baseline Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo Adjusted mean changes in serum K+ from Baseline.
- Secondary Outcome Measures
Name Time Method Hyperkalemia-related Hard Outcomes Endpoints Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo Analyzed using Win Ratio approach with the following hierarchical components:
1. Time to CV death
2. Total number of CV hospitalizations
3. Total number of hyperkalemia toxicity events with serum K+ \>6.5 mEq/l
4. Total number of hyperkalemia events with serum K+ \>6.0-6.5 mEq/l
5. Total number of hyperkalemia events with serum K+ \>5.0 mEq/l
MHTE=More hyperkalemia toxicity events; MHE=More hyperkalemia events; CV=CardiovascularRAASi Use Score Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo RAASi use score (0 to 8 points) analyzed using the Win Ratio approach for each pair of participants with the following additive components:
1. All-cause death
2. Occurrence of a CV hospitalization
3. HF medication use and dose for i) an ACEi/ARB/ARNi, ii) a MRA, and iii) a beta-blocker
Each participant in each comparison can have 0-8 points and all participants are compared using this score at the respective appropriate follow-up time point.
RAASi=renin-angiotensin-aldosterone system inhibitor; ACEi=angiotensin converting enzyme inhibitor; ARB=angiotensin receptor blocker; ARNi=angiotensin receptor/neprilysin inhibitor; MRA=mineralocorticoid receptor antagonist.CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time From Day 1/Baseline to week 90 Cumulative incidence of the first event of hyperkalemia with a serum K+ value \>5.5 mEq/l taking death as competing and calculated as CIF Estimates (95% CI) over time.
Aalen-Johansen estimators of the cumulative incidence function with death as a competing event.
CIF = cumulative incidence function; mEq/l = Milliequivalents Per LiterCIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time From Day 1/Baseline to week 102 Cumulative incidence of the reduction of the MRA dose below target dose calculated as CIF Estimates (95% CI) over time.
Note: The reduction below the MRA target dose must last for at least 14 days (orless if at the end of study) to confirm this endpoint.
CIF = cumulative incidence function; mEq/l = Milliequivalents Per LiterInvestigator-reported Events of Hyperkalemia Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo Participant's follow-up is from the date of the first dose of randomized study medication up to the participant's end of study date or 24 Jun 2021, whichever comes first.
Annualized event rate per 100 subject-years= The total number of events for all subjects in the treatment group divided by the total subject-years of follow-up in that treatment group multiplied by 100.
Trial Locations
- Locations (415)
Investigator Site 11-088
🇺🇸Haddon Heights, New Jersey, United States
Investigator Site 11-148
🇺🇸New Brunswick, New Jersey, United States
Investigator Site 11-054
🇺🇸Linden, New Jersey, United States
Investigator Site 11-110
🇺🇸Greenville, South Carolina, United States
Investigator Site 11-119
🇺🇸Lancaster, South Carolina, United States
Investigator Site 11-133
🇺🇸Rock Hill, South Carolina, United States
Investigator Site 11-142
🇺🇸Memphis, Tennessee, United States
Investigator Site 11-083
🇺🇸Memphis, Tennessee, United States
Investigator Site 21-007
🇦🇷Ciudadela, Buenos Aires, Argentina
Investigator Site 21-004
🇦🇷San Nicolás, Buenos Aires, Argentina
Investigator Site 21-021
🇦🇷Córdoba, Cordoba, Argentina
Investigator Site 21-019
🇦🇷Mar Del Plata, Provincia De Buenos Aires, Argentina
Investigator Site 21-003
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Investigator Site 21-018
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Investigator Site 21-008
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Investigator Site 21-017
🇦🇷Salta, Argentina
Investigator Site 21-005
🇦🇷San Luis, Argentina
Investigator Site 21-009
🇦🇷Santa Fe, Argentina
Investigator Site 44-001
🇧🇪Ghent, Oost Vlaanderen, Belgium
Investigator Site 44-005
🇧🇪Aalst, Belgium
Investigator Site 44-009
🇧🇪Brussels, Belgium
Investigator Site 44-007
🇧🇪Leuven, Belgium
Investigator Site 44-010
🇧🇪Roeselare, Belgium
Investigator Site 22-019
🇧🇷Fortaleza, Ceará, Brazil
Investigator Site 61-004
🇧🇬Plovdiv, Bulgaria
Investigator Site 22-020
🇧🇷São José Do Rio Preto, São Paulo, Brazil
Investigator Site 12-006
🇨🇦Sherbrooke, Quebec, Canada
Investigator Site 36-002
🇳🇱's-Hertogenbosch, Netherlands
Investigator Site 36-014
🇳🇱Hoorn, Netherlands
Investigator Site 65-014
🇵🇱Katowice, Poland
Investigator Site 65-001
🇵🇱Łódź, Poland
Investigator Site 65-018
🇵🇱Łódź, Poland
Investigator Site 66-005
🇷🇺Penza, Russian Federation
Investigator Site 66-007
🇷🇺Perm, Russian Federation
Investigator Site 66-013
🇷🇺Saint Petersburg, Russian Federation
Investigator Site 66-003
🇷🇺Saint Petersburg, Russian Federation
Investigator Site 67-007
🇷🇸Niška Banja, Serbia
Investigator Site 67-001
🇷🇸Sremska Kamenica, Serbia
Investigator Site 68-015
🇺🇦Kyiv, Ukraine
Investigator Site 68-013
🇺🇦Kyiv, Ukraine
Investigator Site 68-001
🇺🇦Kharkiv, Ukraine
Investigator Site 68-010
🇺🇦Kharkiv, Ukraine
Investigator Site 68-007
🇺🇦Kyiv, Ukraine
Investigator Site 63-004
🇬🇪Tbilisi, Georgia
Investigator Site 11-132
🇺🇸Boston, Massachusetts, United States
Investigator Site 11-135
🇺🇸San Diego, California, United States
Investigator Site 11-086
🇺🇸San Diego, California, United States
Investigator Site 11-125
🇺🇸Miami, Florida, United States
Investigator Site 11-005
🇺🇸Miami, Florida, United States
Investigator Site 11-049
🇺🇸Las Vegas, Nevada, United States
Investigator Site 11-140
🇺🇸Houston, Texas, United States
Investigator Site 11-156
🇺🇸Houston, Texas, United States
Investigator Site 11-147
🇺🇸San Antonio, Texas, United States
Investigator Site 22-005
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Investigator Site 11-153
🇺🇸Phoenix, Arizona, United States
Investigator Site 11-145
🇺🇸North Las Vegas, Nevada, United States
Investigator Site 32-012
🇫🇷Toulouse, France
Investigator Site 32-016
🇫🇷Valenciennes, France
Investigator Site 32-008
🇫🇷Paris, France
Investigator Site 32-003
🇫🇷Pau, France
Investigator Site 11-174
🇺🇸Fremont, California, United States
Investigator Site 11-136
🇺🇸Fresno, California, United States
Investigator Site 11-052
🇺🇸Bakersfield, California, United States
Investigator Site 11-111
🇺🇸Laguna Hills, California, United States
Investigator Site 11-017
🇺🇸Long Beach, California, United States
Investigator Site 11-122
🇺🇸Medley, Florida, United States
Investigator Site 11-097
🇺🇸Tucson, Arizona, United States
Investigator Site 11-162
🇺🇸La Jolla, California, United States
Investigator Site 11-102
🇺🇸Huntington Beach, California, United States
Investigator Site 11-035
🇺🇸Pasadena, California, United States
Investigator Site 11-164
🇺🇸Greenacres City, Florida, United States
Investigator Site 11-032
🇺🇸North Miami Beach, Florida, United States
Investigator Site 11-101
🇺🇸Stockton, California, United States
Investigator Site 11-047
🇺🇸Thousand Oaks, California, United States
Investigator Site 11-057
🇺🇸Van Nuys, California, United States
Investigator Site 11-078
🇺🇸Homestead, Florida, United States
Investigator Site 11-004
🇺🇸Jacksonville, Florida, United States
Research Site 11-002
🇺🇸Miami Lakes, Florida, United States
Investigator Site 11-179
🇺🇸Jacksonville, Florida, United States
Research Site 11-001
🇺🇸Miami Lakes, Florida, United States
Investigator Site 11-115
🇺🇸Miami, Florida, United States
Investigator Site 11-031
🇺🇸Arlington Heights, Illinois, United States
Investigator Site 11-144
🇺🇸Pompano Beach, Florida, United States
Investigator Site 11-051
🇺🇸Hazel Crest, Illinois, United States
Investigator Site 11-099
🇺🇸Tamarac, Florida, United States
Investigator Site 11-015
🇺🇸Columbus, Georgia, United States
Investigator Site 11-069
🇺🇸Richmond, Indiana, United States
Investigator Site 11-109
🇺🇸Atlanta, Georgia, United States
Investigator Site 11-141
🇺🇸Macon, Georgia, United States
Investigator Site 11-117
🇺🇸Merrillville, Indiana, United States
Investigator Site 11-071
🇺🇸Lincoln, Nebraska, United States
Investigator Site 11-123
🇺🇸Detroit, Michigan, United States
Investigator Site 11-076
🇺🇸Rochester, Michigan, United States
Investigator Site 11-151
🇺🇸Brooklyn, New York, United States
Investigator Site 11-074
🇺🇸Bartlesville, Oklahoma, United States
Investigator Site 11-018
🇺🇸Greenville, North Carolina, United States
Investigator Site 11-152
🇺🇸Chattanooga, Tennessee, United States
Investigator Site 11-149
🇺🇸Columbus, Ohio, United States
Investigator Site 11-075
🇺🇸Charlotte, North Carolina, United States
Investigator Site 11-064
🇺🇸Lorain, Ohio, United States
Investigator Site 11-053
🇺🇸Richmond Hill, New York, United States
Investigator Site 11-104
🇺🇸Allen, Texas, United States
Investigator Site 11-092
🇺🇸Dallas, Texas, United States
Investigator Site 11-178
🇺🇸Salt Lake City, Utah, United States
Investigator Site 11-124
🇺🇸Oklahoma City, Oklahoma, United States
Investigator Site 11-098
🇺🇸Greenwood, South Carolina, United States
Investigator Site 11-188
🇺🇸Norfolk, Virginia, United States
Investigator Site 11-042
🇺🇸Marion, Ohio, United States
Investigator Site 11-091
🇺🇸Jackson, Tennessee, United States
Investigator Site 11-165
🇺🇸Erie, Pennsylvania, United States
Investigator Site 11-185
🇺🇸Allen, Texas, United States
Investigator Site 11-134
🇺🇸Tullahoma, Tennessee, United States
Investigator Site 11-034
🇺🇸Katy, Texas, United States
Investigator Site 21-006
🇦🇷Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina
Investigator Site 11-085
🇺🇸San Antonio, Texas, United States
Investigator Site 11-029
🇺🇸Lampasas, Texas, United States
Investigator Site 11-161
🇺🇸Sugar Land, Texas, United States
Investigator Site 21-020
🇦🇷Ramos Mejía, Buenos Aires, Argentina
Investigator Site 21-015
🇦🇷Villa María, Cordoba, Argentina
Investigator Site 21-011
🇦🇷Córdoba, Cordoba, Argentina
Investigator Site 44-003
🇧🇪Genk, Belgium
Investigator Site 21-014
🇦🇷Córdoba, Cordoba, Argentina
Investigator Site 21-010
🇦🇷San Miguel De Tucumán, Tucuman, Argentina
Investigator Site 44-008
🇧🇪Hasselt, Belgium
Investigator Site 44-006
🇧🇪Liège, Belgium
Investigator Site 44-002
🇧🇪Mechelen, Antwerp, Belgium
Investigator Site 22-021
🇧🇷Salvador, Bahia, Brazil
Investigator Site 22-011
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Investigator Site 22-013
🇧🇷Fortaleza, Ceará, Brazil
Investigator Site 61-002
🇧🇬Pleven, Bulgaria
Investigator Site 22-004
🇧🇷Uberlândia, Minas Gerais, Brazil
Investigator Site 61-010
🇧🇬Ruse, Bulgaria
Investigator Site 22-023
🇧🇷Brasília, Distrito Federal, Brazil
Investigator Site 22-010
🇧🇷Campina Grande Do Sul, Paraná, Brazil
Investigator Site 22-017
🇧🇷Blumenau, SC, Brazil
Investigator Site 22-012
🇧🇷Vitória, Espirito Santo, Brazil
Investigator Site 22-003
🇧🇷Porto Alegre, RS, Brazil
Investigator Site 22-015
🇧🇷Porto Alegre, RS, Brazil
Investigator Site 22-007
🇧🇷Aracaju, Sergipe, Brazil
Investigator Site 22-024
🇧🇷Rio De Janeiro, Brazil
Investigator Site 22-016
🇧🇷Campinas, São Paulo, Brazil
Investigator Site 22-018
🇧🇷Ribeirão Preto, São Paulo, Brazil
Investigator Site 32-004
🇫🇷Paris, France
Investigator Site 61-003
🇧🇬Burgas, Bulgaria
Investigator Site 32-002
🇫🇷La Tronche, France
Investigator Site 32-017
🇫🇷Paris, France
Investigator Site 32-014
🇫🇷Lille, France
Investigator Site 32-015
🇫🇷Poitiers, France
Investigator Site 22-014
🇧🇷São Paulo, Brazil
Investigator Site 62-017
🇨🇿Havířov, Czechia
Investigator Site 62-016
🇨🇿Uherské Hradiště, Czechia
Investigator Site 12-005
🇨🇦Winnipeg, Manitoba, Canada
Investigator Site 22-022
🇧🇷São Paulo, Brazil
Investigator Site 61-005
🇧🇬Sofia, Bulgaria
Investigator Site 61-006
🇧🇬Sofia, Bulgaria
Investigator Site 12-013
🇨🇦Saint John's, Newfoundland and Labrador, Canada
Investigator Site 61-009
🇧🇬Sofia, Bulgaria
Investigator Site 61-008
🇧🇬Sofia, Bulgaria
Investigator Site 62-005
🇨🇿Havlíčkův Brod, Czechia
Investigator Site 12-008
🇨🇦Cambridge, Ontario, Canada
Investigator Site 62-013
🇨🇿Liberec, Czechia
Investigator Site 12-012
🇨🇦London, Ontario, Canada
Investigator Site 12-009
🇨🇦Greenfield Park, Quebec, Canada
Investigator Site 32-020
🇫🇷Lyon, France
Investigator Site 32-010
🇫🇷Bordeaux, France
Investigator Site 32-005
🇫🇷Montpellier, France
Investigator Site 32-013
🇫🇷Reims, France
Investigator Site 32-019
🇫🇷Rouen, France
Investigator Site 32-018
🇫🇷Saint-Brieuc, France
Investigator Site 62-004
🇨🇿Bílina, Czechia
Investigator Site 32-009
🇫🇷Tourcoing, France
Investigator Site 62-019
🇨🇿Brno, Czechia
Investigator Site 62-018
🇨🇿Náchod, Czechia
Investigator Site 32-001
🇫🇷Nancy, France
Investigator Site 62-011
🇨🇿Slaný, Czechia
Investigator Site 63-011
🇬🇪Tbilisi, Georgia
Investigator Site 32-011
🇫🇷Valenciennes, France
Investigator Site 32-007
🇫🇷Paris, France
Investigator Site 32-006
🇫🇷Toulon, France
Investigator Site 33-008
🇩🇪Greifswald, Mecklenburg-Vorpommern, Germany
Investigator Site 63-002
🇬🇪Tbilisi, Georgia
Investigator Site 63-010
🇬🇪Tbilisi, Georgia
Investigator Site 63-003
🇬🇪Tbilisi, Georgia
Investigator Site 63-001
🇬🇪Tbilisi, Georgia
Investigator Site 33-013
🇩🇪Berlin, Germany
Investigator Site 33-023
🇩🇪Bad Oeynhausen, Germany
Investigator Site 64-002
🇭🇺Budapest, Hungary
Investigator Site 64-001
🇭🇺Kecskemét, Hungary
Investigator Site 33-024
🇩🇪Minden, Germany
Investigator Site 35-010
🇮🇱Nahariya, Israel
Investigator Site 34-002
🇮🇹Bergamo, Italy
Investigator Site 34-003
🇮🇹Roma, Italy
Investigator Site 36-009
🇳🇱Dirksland, Netherlands
Investigator Site 23-011
🇲🇽Oaxaca de Juarez, Oaxaca, Mexico
Investigator Site 36-006
🇳🇱Blaricum, Netherlands
Investigator Site 23-010
🇲🇽San Pedro Garza Garcia, Nuevo Léon, Mexico
Investigator Site 36-007
🇳🇱Ede, Netherlands
Investigator Site 36-003
🇳🇱Rotterdam, South Holland, Netherlands
Investigator Site 23-006
🇲🇽Xalapa, Veracruz, Mexico
Investigator Site 23-002
🇲🇽Culiacán, Sinaloa, Mexico
Investigator Site 23-004
🇲🇽Guadalajara, Jalisco, Mexico
Investigator Site 36-012
🇳🇱Amstelveen, Netherlands
Investigator Site 36-001
🇳🇱Groningen, Netherlands
Investigator Site 23-001
🇲🇽Santiago De Querétaro, Querétaro, Mexico
Investigator Site 65-010
🇵🇱Wrocław, Poland
Investigator Site 67-008
🇷🇸Belgrade, Serbia
Investigator Site 67-005
🇷🇸Niš, Serbia
Investigator Site 66-016
🇷🇺Kazan, Russian Federation
Investigator Site 66-010
🇷🇺Kemerovo, Russian Federation
Investigator Site 67-004
🇷🇸Belgrade, Serbia
Investigator Site 66-017
🇷🇺Moscow, Russian Federation
Investigator Site 67-002
🇷🇸Belgrade, Serbia
Investigator Site 37-002
🇪🇸Barcelona, Spain
Investigator Site 37-011
🇪🇸Majadahonda, Madrid, Spain
Investigator Site 37-005
🇪🇸Santiago De Compostela, La Coruña, Spain
Investigator Site 37-016
🇪🇸La Laguna, Tenerife, Spain
Investigator Site 37-026
🇪🇸Madrid, Spain
Investigator Site 37-012
🇪🇸Alicante, Spain
Investigator Site 68-008
🇺🇦Kharkiv, Novobavarskiy, Ukraine
Investigator Site 68-005
🇺🇦Ivano-Frankivs'k, Ukraine
Investigator Site 39-003
🇬🇧Scunthorpe, North Lincolshire, United Kingdom
Investigator Site 39-005
🇬🇧Dudley, West Midlands, United Kingdom
Investigator Site 39-009
🇬🇧Barnsley, United Kingdom
Investigator Site 67-003
🇷🇸Šabac, Serbia
Investigator Site 37-010
🇪🇸Castellón De La Plana, Castellon, Spain
Investigator Site 37-006
🇪🇸Madrid, Spain
Investigator Site 68-011
🇺🇦Kharkiv, Ukraine
Investigator Site 37-009
🇪🇸Valencia, Spain
Investigator Site 37-013
🇪🇸Sevilla, Spain
Investigator Site 39-011
🇬🇧Leicester, United Kingdom
Investigator Site 37-014
🇪🇸Palma De Mallorca, Baleares, Spain
Investigator Site 37-004
🇪🇸Madrid, Spain
Investigator Site 37-001
🇪🇸Manises, Valencia, Spain
Investigator Site 37-003
🇪🇸Barcelona, Cataluña, Spain
Investigator Site 68-017
🇺🇦Dnipro, Ukraine
Investigator Site 37-025
🇪🇸La Coruña, Spain
Investigator Site 68-009
🇺🇦Ivano-Frankivs'k, Ukraine
Investigator Site 68-003
🇺🇦Kyiv, Ukraine
Investigator Site 68-016
🇺🇦Zaporizhzhya, Ukraine
Investigator Site 68-004
🇺🇦Zhytomyr, Ukraine
Investigator Site 68-002
🇺🇦Kharkiv, Ukraine
Investigator Site 68-012
🇺🇦Kyiv, Ukraine
Investigator Site 68-006
🇺🇦Lviv, Ukraine
Investigator Site 39-012
🇬🇧Harlow, Essex, United Kingdom
Investigator Site 68-014
🇺🇦Vinnytsia, Ukraine
Investigator Site 39-016
🇬🇧High Wycombe, United Kingdom
Investigator Site 39-015
🇬🇧London, United Kingdom
Investigator Site 39-008
🇬🇧Inverness, United Kingdom
Investigator Site 39-010
🇬🇧North Shields, United Kingdom
Investigator Site 39-013
🇬🇧Liverpool, United Kingdom
Investigator Site 39-007
🇬🇧Swansea, United Kingdom
Investigator Site 22-002
🇧🇷Porto Alegre, RS, Brazil
Investigator Site 33-012
🇩🇪Heilbronn, Germany
Investigator Site 33-019
🇩🇪Frankfurt, Germany
Investigator Site 33-007
🇩🇪Frankfurt, Germany
Investigator Site 33-004
🇩🇪Erfurt, Germany
Investigator Site 11-041
🇺🇸Huntsville, Alabama, United States
Investigator Site 11-080
🇺🇸Alexander City, Alabama, United States
Investigator Site 37-008
🇪🇸Valencia, Spain
Investigator Site 37-015
🇪🇸Badalona, Spain
Investigator Site 37-018
🇪🇸Huelva, Spain
Investigator Site 37-017
🇪🇸Málaga, Spain
Investigator Site 37-024
🇪🇸Marbella, Malaga, Spain
Investigator Site 37-023
🇪🇸Lleida, Spain
Investigator Site 62-001
🇨🇿Praha, Czechia
Investigator Site 62-010
🇨🇿Mariánské Lázně, Czechia
Investigator Site 62-015
🇨🇿Litovel, Czechia
Investigator Site 62-012
🇨🇿Praha, Czechia
Investigator Site 62-009
🇨🇿Praha, Czechia
Investigator Site 11-082
🇺🇸Hershey, Pennsylvania, United States
Investigator Site 11-090
🇺🇸Tampa, Florida, United States
Investigator Site 11-163
🇺🇸Tampa, Florida, United States
Investigator Site 11-169
🇺🇸Portland, Oregon, United States
Investigator Site 11-045
🇺🇸Milwaukee, Wisconsin, United States
Investigator Site 11-048
🇺🇸La Mesa, California, United States
Investigator Site 11-058
🇺🇸West Hills, California, United States
Investigator Site 11-176
🇺🇸Dallas, Texas, United States
Investigator Site 11-157
🇺🇸Lumberton, North Carolina, United States
Investigator Site 37-007
🇪🇸Barcelona, Spain
Investigator Site 37-020
🇪🇸Madrid, Spain
Investigator Site 37-022
🇪🇸Murcia, Spain
Investigator Site 11-089
🇺🇸Houston, Texas, United States
Investigator Site 11-046
🇺🇸McKinney, Texas, United States
Investigator Site 11-072
🇺🇸Gonzales, Texas, United States
Investigator Site 11-146
🇺🇸Houston, Texas, United States
Investigator Site 37-021
🇪🇸Madrid, Spain
Investigator Site 11-112
🇺🇸Santa Ana, California, United States
Investigator Site 66-011
🇷🇺Moscow, Russian Federation
Investigator Site 11-023
🇺🇸Columbia, Maryland, United States
Investigator Site 12-010
🇨🇦Newmarket, Ontario, Canada
Investigator Site 34-004
🇮🇹Milano, Italy
Investigator Site 11-128
🇺🇸Northridge, California, United States
Investigator Site 11-095
🇺🇸Aurora, Colorado, United States
Investigator Site 11-106
🇺🇸Boynton Beach, Florida, United States
Investigator Site 11-003
🇺🇸Doral, Florida, United States
Investigator Site 11-168
🇺🇸Altamonte Springs, Florida, United States
Investigator Site 11-028
🇺🇸Brandon, Florida, United States
Investigator Site 11-177
🇺🇸Pembroke Pines, Florida, United States
Investigator Site 11-063
🇺🇸Peoria, Illinois, United States
Investigator Site 11-129
🇺🇸Munster, Indiana, United States
Investigator Site 11-027
🇺🇸Baltimore, Maryland, United States
Investigator Site 11-061
🇺🇸Owensboro, Kentucky, United States
Investigator Site 11-137
🇺🇸Peoria, Illinois, United States
Investigator Site 11-183
🇺🇸Opelousas, Louisiana, United States
Investigator Site 11-121
🇺🇸Livonia, Michigan, United States
Investigator Site 11-022
🇺🇸West Monroe, Louisiana, United States
Investigator Site 11-068
🇺🇸Jackson, Mississippi, United States
Investigator Site 11-094
🇺🇸Saint Louis, Missouri, United States
Investigator Site 11-189
🇺🇸Rochester, Michigan, United States
Investigator Site 11-107
🇺🇸Newark, New Jersey, United States
Investigator Site 11-116
🇺🇸Albuquerque, New Mexico, United States
Investigator Site 11-073
🇺🇸Buffalo, New York, United States
Investigator Site 11-126
🇺🇸Brooklyn, New York, United States
Investigator Site 11-120
🇺🇸Charlotte, North Carolina, United States
Investigator Site 11-056
🇺🇸Hillsboro, Oregon, United States
Investigator Site 11-040
🇺🇸Manhasset, New York, United States
Investigator Site 11-021
🇺🇸Stony Brook, New York, United States
Investigator Site 11-081
🇺🇸Staten Island, New York, United States
Investigator Site 11-170
🇺🇸Denison, Texas, United States
Investigator Site 11-070
🇺🇸Amarillo, Texas, United States
Investigator Site 11-060
🇺🇸Fort Worth, Texas, United States
Investigator Site 11-158
🇺🇸Norfolk, Virginia, United States
Investigator Site 11-160
🇺🇸Webster, Texas, United States
Investigator Site 11-065
🇺🇸Morgantown, West Virginia, United States
Investigator Site 21-012
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Investigator Site 22-008
🇧🇷Canoas, Rio Grande Do Sul, Brazil
Investigator Site 44-004
🇧🇪Yvoir, Belgium
Investigator Site 22-009
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Investigator Site 22-025
🇧🇷Porto Alegre, RS, Brazil
Investigator Site 12-002
🇨🇦Toronto, Ontario, Canada
Investigator Site 64-009
🇭🇺Budapest, Hungary
Investigator Site 12-004
🇨🇦Trois-Rivières, Quebec, Canada
Investigator Site 63-012
🇬🇪Batumi, Georgia
Investigator Site 35-001
🇮🇱Jerusalem, Israel
Investigator Site 63-007
🇬🇪Tbilisi, Georgia
Investigator Site 63-009
🇬🇪Tbilisi, Georgia
Investigator Site 63-006
🇬🇪Tbilisi, Georgia
Investigator Site 63-008
🇬🇪Tbilisi, Georgia
Investigator Site 63-005
🇬🇪Tbilisi, Georgia
Investigator Site 33-011
🇩🇪Coburg, Bavarian, Germany
Investigator Site 33-020
🇩🇪Berlin, Germany
Investigator Site 33-006
🇩🇪Homburg, Saar, Germany
Investigator Site 33-015
🇩🇪Bielefeld, Germany
Investigator Site 33-016
🇩🇪Bremen, Germany
Investigator Site 33-005
🇩🇪Hamburg, Germany
Investigator Site 33-001
🇩🇪Essen, Germany
Investigator Site 33-002
🇩🇪Halle, Germany
Investigator Site 33-018
🇩🇪Gießen, Germany
Investigator Site 33-022
🇩🇪Hanover, Germany
Investigator Site 33-021
🇩🇪Leipzig, Germany
Investigator Site 33-003
🇩🇪Würzburg, Germany
Investigator Site 33-017
🇩🇪Kiel, Germany
Investigator Site 64-007
🇭🇺Kistarcsa, Hungary
Investigator Site 64-010
🇭🇺Budapest, Hungary
Investigator Site 33-010
🇩🇪Leverkusen, Germany
Investigator Site 33-014
🇩🇪Nürnberg, Germany
Investigator Site 35-009
🇮🇱Be'er Ya'aqov, Israel
Investigator Site 35-003
🇮🇱Hadera, Israel
Investigator Site 64-005
🇭🇺Nyiregyhaza, Hungary
Investigator Site 35-006
🇮🇱Haifa, Israel
Investigator Site 35-007
🇮🇱Haifa, Israel
Investigator Site 64-006
🇭🇺Budapest, Hungary
Investigator Site 35-008
🇮🇱Ashqelon, Israel
Investigator Site 35-002
🇮🇱H̱olon, Israel
Investigator Site 35-013
🇮🇱Ramat Gan, Israel
Investigator Site 34-009
🇮🇹Cona, Italy
Investigator Site 35-005
🇮🇱Jerusalem, Israel
Investigator Site 35-014
🇮🇱Jerusalem, Israel
Investigator Site 35-011
🇮🇱Petah tikva, Israel
Investigator Site 34-005
🇮🇹Ancona, Italy
Investigator Site 35-012
🇮🇱Safed, Israel
Investigator Site 35-016
🇮🇱Tiberias, Israel
Investigator Site 34-007
🇮🇹Brescia, Italy
Investigator Site 34-001
🇮🇹Caserta, Italy
Investigator Site 34-013
🇮🇹San Bonifacio, Italy
Investigator Site 34-014
🇮🇹Foggia, Italy
Investigator Site 34-010
🇮🇹Genova, Italy
Investigator Site 34-012
🇮🇹Piacenza, Italy
Investigator Site 23-007
🇲🇽Cuauhtémoc, Ciudad De Mexico, Mexico
Investigator Site 23-005
🇲🇽Delegación Gustavo A. Madero, Ciudad De Mexico, Mexico
Investigator Site 23-012
🇲🇽Guadalajara, Jalisco, Mexico
Investigator Site 36-010
🇳🇱Schiedam, Netherlands
Investigator Site 36-015
🇳🇱Dordrecht, Netherlands
Investigator Site 36-013
🇳🇱Helmond, Netherlands
Investigator Site 36-004
🇳🇱Tilburg, Netherlands
Investigator Site 36-011
🇳🇱Utrecht, Netherlands
Investigator Site 65-012
🇵🇱Kędzierzyn-Koźle, Poland
Investigator Site 65-007
🇵🇱Białystok, Poland
Investigator Site 65-015
🇵🇱Ostrowiec Świętokrzyski, Poland
Investigator Site 65-021
🇵🇱Pomorskie, Poland
Investigator Site 65-019
🇵🇱Olsztyn, Poland
Investigator Site 65-003
🇵🇱Poznań, Poland
Investigator Site 65-008
🇵🇱Rzeszów, Poland
Investigator Site 65-020
🇵🇱Poznań, Poland
Investigator Site 65-005
🇵🇱Wrocław, Poland
Investigator Site 65-011
🇵🇱Zgierz, Poland
Investigator Site 66-014
🇷🇺Izhevsk, Udmurt Republic, Russian Federation
Investigator Site 66-008
🇷🇺Chelyabinsk, Russian Federation
Investigator Site 66-001
🇷🇺Ekaterinburg, Russian Federation
Investigator Site 66-004
🇷🇺Moscow, Russian Federation
Investigator Site 66-015
🇷🇺Moscow, Russian Federation
Investigator Site 66-002
🇷🇺Novosibirsk, Russian Federation
Investigator Site 66-012
🇷🇺Petrozavodsk, Russian Federation
Investigator Site 66-018
🇷🇺Ryazan', Russian Federation
Investigator Site 66-009
🇷🇺Tver, Russian Federation
Investigator Site 67-010
🇷🇸Belgrade, Serbia
Investigator Site 39-004
🇬🇧York, United Kingdom
Investigator Site 11-044
🇺🇸Sacramento, California, United States
Investigator Site 11-154
🇺🇸Kansas City, Missouri, United States
Investigator Site 11-171
🇺🇸Orlando, Florida, United States
Investigator Site 11-025
🇺🇸Orlando, Florida, United States
Investigator Site 11-087
🇺🇸Orlando, Florida, United States
Investigator Site 11-138
🇺🇸Gainesville, Florida, United States
Investigator Site 11-127
🇺🇸Bronx, New York, United States
Investigator Site 11-187
🇺🇸Toledo, Ohio, United States