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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01920711




Registration number
NCT01920711
Ethics application status
Date submitted
8/08/2013
Date registered
12/08/2013
Date last updated
29/05/2019

Titles & IDs
Public title
Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction
Scientific title
A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients (NYHA Class II-IV) With Preserved Ejection Fraction
Secondary ID [1] 0 0
2013-001747-31
Secondary ID [2] 0 0
CLCZ696D2301
Universal Trial Number (UTN)
Trial acronym
PARAGON-HF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure With Preserved Ejection Fraction 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LCZ696
Treatment: Drugs - Valsartan

Experimental: LCZ696 - Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria. Target dose of LCZ696 during the double blind period is 200 mg b.i.d.

Active Comparator: Valsartan - Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria. Target dose of Valsartan during the double blind period is 160 mg b.i.d.


Treatment: Drugs: LCZ696
LCZ696 50mg, 100mg and 200 mg dosage strengths will be available for dose adjustments.

Treatment: Drugs: Valsartan
Valsartan 40mg, 80mg and 160mg dosage strengths will be available for dose adjustments.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cumulative number of primary composite events of cardiovascular (CV) death and total (first and recurrent) HF hospitalizations. - The primary objective of this study is to compare LCZ696 to valsartan in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF hospitalizations, in HF patients (New York Heart Association [NYHA] Class II-IV) with preserved ejection fraction (left ventricular ejection fraction [LVEF] =45%). The treatment arm with the lower rate of events will be deemed as having a successful response.
Timepoint [1] 0 0
Total follow up time (up to 57 months)
Secondary outcome [1] 0 0
Change in the clinical summary score from baseline to Month 8 by Kansas City Cardiomyopathy Questionnaire (KCCQ) - Evaluation of change from baseline to month 8 in KCCQ a most sensitive, specific, and responsive health-related quality of life measure for heart failure symptoms and physical limitations.
Timepoint [1] 0 0
Baseline, 8 months
Secondary outcome [2] 0 0
Change from baseline to Month 8 in New York Heart Association (NYHA) functional class - Evaluation of change from baseline to Month 8 in NYHA functional class, a well established grading scale used to classify a HF patients' level of functionality based on the signs and symptoms of HF exhibited by the patient.
Timepoint [2] 0 0
Baseline, 8 months
Secondary outcome [3] 0 0
Time to first occurance of a composite renal endpoint - Evaluate significance of outcome modifying agents in worsening renal dysfunction.
Composite renal endpoint defined as follows:
renal death, or
reaching ESRD, or
=50% decline in eGFR relative to baseline
Timepoint [3] 0 0
Total follow up time (up to 57 months)
Secondary outcome [4] 0 0
Time to all-cause mortality - Evaluation of the time to all cause death.
Timepoint [4] 0 0
Total follow up time (up to 57 months)

Eligibility
Key inclusion criteria
- Left ventricular ejection fraction (LVEF) =45% by echo during screening epoch or
within 6 months prior to study entry.

- Symptom(s) of heart failure (HF) and requiring treatment with diuretic(s) for HF at
least 30 days prior to study entry.

- Current symptom(s) of HF

- Structural heart disease (left atrial enlargement or left ventricular hypertrophy)
documented by echocardiogram.

- Elevated NT-proBNP
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any prior measurement of LVEF < 40%.

- Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within
3 months , or urgent percutaneous coronary intervention within 3 months or and
elective PCI within 30 days prior to entry.

- Any clinical event within the 6 months prior to entry could have reduced the LVEF
(e.g., MI, CABG), unless an echo measurement performed after the event confirms a LVEF
=45%.

- Current acute decompensated HF requiring therapy.

- Patients who require treatment with 2 or more of the following: an angiotensin
converting enzyme inhibitor (ACEI), an angiotensin receptor blocker (ARB) or a renin
inhibitor.

- Alternative reason for shortness of breath such as: significant pulmonary disease or
severe COPD, hemoglobin (Hgb) <10 g/dl, or body mass index (BMI) > 40 kg/m2.

- Systolic blood pressure (SBP) = 180 mmHg at entry, or SBP >150 mmHg and <180 mmHg at
entry unless the patient is receiving 3 or more antihypertensive drugs, or SBP < 110
mmHg at entry.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
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NSW,QLD,SA,VIC
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Novartis Investigative Site - Gosford
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2250 - Gosford
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2109 - North Ryde
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4066 - Auchenflower
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4215 - Southport
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5041 - Bedford Park
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3076 - Epping
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3220 - Geelong
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Germany
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Germany
State/province [210] 0 0
Nurnberg
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Germany
State/province [211] 0 0
Oschatz
Country [212] 0 0
Germany
State/province [212] 0 0
Papenburg
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Germany
State/province [213] 0 0
Reinfeld
Country [214] 0 0
Germany
State/province [214] 0 0
Riesa
Country [215] 0 0
Germany
State/province [215] 0 0
Rodgau
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Germany
State/province [216] 0 0
Siegen
Country [217] 0 0
Germany
State/province [217] 0 0
Ulm
Country [218] 0 0
Germany
State/province [218] 0 0
Vilshofen
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Germany
State/province [219] 0 0
Wangen
Country [220] 0 0
Germany
State/province [220] 0 0
Wermsdorf
Country [221] 0 0
Germany
State/province [221] 0 0
Weyhe
Country [222] 0 0
Germany
State/province [222] 0 0
Witten
Country [223] 0 0
Germany
State/province [223] 0 0
Wuerzburg
Country [224] 0 0
Greece
State/province [224] 0 0
Attica
Country [225] 0 0
Greece
State/province [225] 0 0
GR
Country [226] 0 0
Greece
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Athens
Country [227] 0 0
Greece
State/province [227] 0 0
Thessaloniki
Country [228] 0 0
Guatemala
State/province [228] 0 0
Guatemala City
Country [229] 0 0
Guatemala
State/province [229] 0 0
Quetzaltenango
Country [230] 0 0
Hungary
State/province [230] 0 0
Budapest
Country [231] 0 0
Hungary
State/province [231] 0 0
Cegled
Country [232] 0 0
Hungary
State/province [232] 0 0
Kistarcsa
Country [233] 0 0
Hungary
State/province [233] 0 0
Mako
Country [234] 0 0
Hungary
State/province [234] 0 0
Nyiregyháza
Country [235] 0 0
Hungary
State/province [235] 0 0
Pecs
Country [236] 0 0
Hungary
State/province [236] 0 0
Pécs
Country [237] 0 0
Hungary
State/province [237] 0 0
Szeged
Country [238] 0 0
Hungary
State/province [238] 0 0
Szekesfehervar
Country [239] 0 0
Hungary
State/province [239] 0 0
Zalaegerszeg
Country [240] 0 0
India
State/province [240] 0 0
Andhra Pradesh
Country [241] 0 0
India
State/province [241] 0 0
Delhi
Country [242] 0 0
India
State/province [242] 0 0
Gujarat
Country [243] 0 0
India
State/province [243] 0 0
Haryana
Country [244] 0 0
India
State/province [244] 0 0
Karnataka
Country [245] 0 0
India
State/province [245] 0 0
Kerala
Country [246] 0 0
India
State/province [246] 0 0
Maharashtra
Country [247] 0 0
India
State/province [247] 0 0
Punjab
Country [248] 0 0
India
State/province [248] 0 0
Rajasthan
Country [249] 0 0
India
State/province [249] 0 0
Tamil NADU
Country [250] 0 0
India
State/province [250] 0 0
Tamil Nadu
Country [251] 0 0
India
State/province [251] 0 0
West Bengal
Country [252] 0 0
India
State/province [252] 0 0
New Delhi
Country [253] 0 0
Israel
State/province [253] 0 0
Hadera
Country [254] 0 0
Israel
State/province [254] 0 0
Haifa
Country [255] 0 0
Israel
State/province [255] 0 0
Lower Galilee
Country [256] 0 0
Israel
State/province [256] 0 0
Nahariya
Country [257] 0 0
Israel
State/province [257] 0 0
Petach Tikva
Country [258] 0 0
Israel
State/province [258] 0 0
Ramat Gan
Country [259] 0 0
Israel
State/province [259] 0 0
Rehovot
Country [260] 0 0
Israel
State/province [260] 0 0
Tel Giborim, Holon
Country [261] 0 0
Italy
State/province [261] 0 0
AO
Country [262] 0 0
Italy
State/province [262] 0 0
AR
Country [263] 0 0
Italy
State/province [263] 0 0
BG
Country [264] 0 0
Italy
State/province [264] 0 0
BO
Country [265] 0 0
Italy
State/province [265] 0 0
BS
Country [266] 0 0
Italy
State/province [266] 0 0
CO
Country [267] 0 0
Italy
State/province [267] 0 0
FE
Country [268] 0 0
Italy
State/province [268] 0 0
IS
Country [269] 0 0
Italy
State/province [269] 0 0
MB
Country [270] 0 0
Italy
State/province [270] 0 0
ME
Country [271] 0 0
Italy
State/province [271] 0 0
MI
Country [272] 0 0
Italy
State/province [272] 0 0
PA
Country [273] 0 0
Italy
State/province [273] 0 0
PC
Country [274] 0 0
Italy
State/province [274] 0 0
PD
Country [275] 0 0
Italy
State/province [275] 0 0
PG
Country [276] 0 0
Italy
State/province [276] 0 0
PV
Country [277] 0 0
Italy
State/province [277] 0 0
RM
Country [278] 0 0
Italy
State/province [278] 0 0
SS
Country [279] 0 0
Italy
State/province [279] 0 0
TS
Country [280] 0 0
Italy
State/province [280] 0 0
TV
Country [281] 0 0
Italy
State/province [281] 0 0
UD
Country [282] 0 0
Italy
State/province [282] 0 0
Va
Country [283] 0 0
Italy
State/province [283] 0 0
VE
Country [284] 0 0
Italy
State/province [284] 0 0
Milano
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Italy
State/province [285] 0 0
Napoli
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Italy
State/province [286] 0 0
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Japan
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Aichi
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Japan
State/province [288] 0 0
Fukuka
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Japan
State/province [289] 0 0
Gifu
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Japan
State/province [290] 0 0
Gunma
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Japan
State/province [291] 0 0
Hyogo
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Japan
State/province [292] 0 0
Ishikawa
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Japan
State/province [293] 0 0
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Japan
State/province [294] 0 0
Kagawa
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Japan
State/province [295] 0 0
Kanagawa
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Japan
State/province [296] 0 0
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Country [297] 0 0
Japan
State/province [297] 0 0
Nara
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Japan
State/province [298] 0 0
Oita
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Japan
State/province [299] 0 0
Saitama
Country [300] 0 0
Japan
State/province [300] 0 0
Shiga
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Japan
State/province [301] 0 0
Tokyo
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Korea, Republic of
State/province [302] 0 0
Bucheon Si
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Korea, Republic of
State/province [303] 0 0
Chungcheongbuk Do
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Korea, Republic of
State/province [304] 0 0
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Korea, Republic of
State/province [305] 0 0
Gyeonggi Do
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Korea, Republic of
State/province [306] 0 0
Gyeonggi-do
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Korea, Republic of
State/province [307] 0 0
Korea
Country [308] 0 0
Korea, Republic of
State/province [308] 0 0
KOR
Country [309] 0 0
Korea, Republic of
State/province [309] 0 0
Daegu
Country [310] 0 0
Korea, Republic of
State/province [310] 0 0
Seoul
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Mexico
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Coahulia
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Mexico
State/province [312] 0 0
Distrito Federal
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Mexico
State/province [313] 0 0
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Mexico
State/province [314] 0 0
Jalisco
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Mexico
State/province [315] 0 0
Queretaro
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Mexico
State/province [316] 0 0
San Luis Potosí
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Mexico
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Mexico
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Mexico
State/province [319] 0 0
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DZ
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Netherlands
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NL
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Netherlands
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PP
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Arnhem
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Netherlands
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Blaricum
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Netherlands
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Den Haag
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Netherlands
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Ede
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Netherlands
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Gouda
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Netherlands
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Groningen
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Netherlands
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Hardenberg
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Netherlands
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Harderwijk
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Netherlands
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Netherlands
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Rotterdam
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Netherlands
State/province [333] 0 0
Sneek
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Netherlands
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Tilburg
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Netherlands
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Zwolle
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Hønefoss
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Loerenskog
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Norway
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Oslo
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Stavanger
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Norway
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Tromsoe
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Lima
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Batangas
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Philippines
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Philippines
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Quezon City
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Poland
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Lodzkie
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Poland
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Gdansk
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Poland
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Gdynia
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Poland
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Grodzisk Mazowiecki
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Poland
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Katowice
Country [350] 0 0
Poland
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Krakow
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Poland
State/province [351] 0 0
Lublin
Country [352] 0 0
Poland
State/province [352] 0 0
Piaseczno
Country [353] 0 0
Poland
State/province [353] 0 0
Sandomierz
Country [354] 0 0
Poland
State/province [354] 0 0
Staszów
Country [355] 0 0
Poland
State/province [355] 0 0
Torun
Country [356] 0 0
Poland
State/province [356] 0 0
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Poland
State/province [357] 0 0
Warszawa
Country [358] 0 0
Poland
State/province [358] 0 0
Zabrze
Country [359] 0 0
Poland
State/province [359] 0 0
Zamosc
Country [360] 0 0
Romania
State/province [360] 0 0
Arges
Country [361] 0 0
Romania
State/province [361] 0 0
District 1
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Romania
State/province [362] 0 0
Jud. Dolj
Country [363] 0 0
Romania
State/province [363] 0 0
Jud. Iasi
Country [364] 0 0
Romania
State/province [364] 0 0
ROM
Country [365] 0 0
Romania
State/province [365] 0 0
Timis
Country [366] 0 0
Romania
State/province [366] 0 0
Arad
Country [367] 0 0
Romania
State/province [367] 0 0
Baia Mare
Country [368] 0 0
Romania
State/province [368] 0 0
Bucharest
Country [369] 0 0
Romania
State/province [369] 0 0
Bucuresti
Country [370] 0 0
Romania
State/province [370] 0 0
Oradea
Country [371] 0 0
Romania
State/province [371] 0 0
Targu Mures
Country [372] 0 0
Romania
State/province [372] 0 0
Timisoara
Country [373] 0 0
Russian Federation
State/province [373] 0 0
Chelyabinsk
Country [374] 0 0
Russian Federation
State/province [374] 0 0
Ekaterinburg
Country [375] 0 0
Russian Federation
State/province [375] 0 0
Ivanovo
Country [376] 0 0
Russian Federation
State/province [376] 0 0
Izhevsk
Country [377] 0 0
Russian Federation
State/province [377] 0 0
Kemerovo
Country [378] 0 0
Russian Federation
State/province [378] 0 0
Kirov
Country [379] 0 0
Russian Federation
State/province [379] 0 0
Moscow
Country [380] 0 0
Russian Federation
State/province [380] 0 0
N.Novgorod
Country [381] 0 0
Russian Federation
State/province [381] 0 0
Perm
Country [382] 0 0
Russian Federation
State/province [382] 0 0
Rostov on Don
Country [383] 0 0
Russian Federation
State/province [383] 0 0
Rostov-on-Don
Country [384] 0 0
Russian Federation
State/province [384] 0 0
Saint Petersburg
Country [385] 0 0
Russian Federation
State/province [385] 0 0
Saint-Petersburg
Country [386] 0 0
Russian Federation
State/province [386] 0 0
Saratov
Country [387] 0 0
Russian Federation
State/province [387] 0 0
Sestroretsk
Country [388] 0 0
Russian Federation
State/province [388] 0 0
Smolensk
Country [389] 0 0
Russian Federation
State/province [389] 0 0
St Petersburg
Country [390] 0 0
Russian Federation
State/province [390] 0 0
St-Petersburg
Country [391] 0 0
Russian Federation
State/province [391] 0 0
St.- Petersburg
Country [392] 0 0
Russian Federation
State/province [392] 0 0
Yaroslavl
Country [393] 0 0
Serbia
State/province [393] 0 0
Belgrade
Country [394] 0 0
Serbia
State/province [394] 0 0
Beograd
Country [395] 0 0
Serbia
State/province [395] 0 0
Niska Banja
Country [396] 0 0
Serbia
State/province [396] 0 0
Nis
Country [397] 0 0
Singapore
State/province [397] 0 0
Singapore
Country [398] 0 0
Slovakia
State/province [398] 0 0
Slovak Republic
Country [399] 0 0
Slovakia
State/province [399] 0 0
Bardejov
Country [400] 0 0
Slovakia
State/province [400] 0 0
Bratislava
Country [401] 0 0
Slovakia
State/province [401] 0 0
Kosice
Country [402] 0 0
Slovakia
State/province [402] 0 0
Levice
Country [403] 0 0
Slovakia
State/province [403] 0 0
Lucenec
Country [404] 0 0
Slovakia
State/province [404] 0 0
Nitra
Country [405] 0 0
Slovakia
State/province [405] 0 0
Nove Zamky
Country [406] 0 0
Slovakia
State/province [406] 0 0
Piestany
Country [407] 0 0
Slovakia
State/province [407] 0 0
Presov
Country [408] 0 0
Slovakia
State/province [408] 0 0
Svidnik
Country [409] 0 0
Slovakia
State/province [409] 0 0
Trebisov
Country [410] 0 0
Slovakia
State/province [410] 0 0
Zilina
Country [411] 0 0
Slovenia
State/province [411] 0 0
Golnik
Country [412] 0 0
Slovenia
State/province [412] 0 0
Ljubljana
Country [413] 0 0
South Africa
State/province [413] 0 0
Eastern Cape
Country [414] 0 0
South Africa
State/province [414] 0 0
Free State
Country [415] 0 0
South Africa
State/province [415] 0 0
Gauteng
Country [416] 0 0
South Africa
State/province [416] 0 0
Kwa-Zulu Natal
Country [417] 0 0
South Africa
State/province [417] 0 0
Western Cape
Country [418] 0 0
South Africa
State/province [418] 0 0
Alberton
Country [419] 0 0
South Africa
State/province [419] 0 0
Bloemfontein
Country [420] 0 0
South Africa
State/province [420] 0 0
Cape Town
Country [421] 0 0
South Africa
State/province [421] 0 0
Durban
Country [422] 0 0
South Africa
State/province [422] 0 0
Johannesburg
Country [423] 0 0
South Africa
State/province [423] 0 0
Pretoria
Country [424] 0 0
South Africa
State/province [424] 0 0
Tongaat
Country [425] 0 0
South Africa
State/province [425] 0 0
Worcester
Country [426] 0 0
Spain
State/province [426] 0 0
Andalucia
Country [427] 0 0
Spain
State/province [427] 0 0
Asturias
Country [428] 0 0
Spain
State/province [428] 0 0
Barcelona
Country [429] 0 0
Spain
State/province [429] 0 0
Cadiz
Country [430] 0 0
Spain
State/province [430] 0 0
Cantabria
Country [431] 0 0
Spain
State/province [431] 0 0
Castilla Y Leon
Country [432] 0 0
Spain
State/province [432] 0 0
Cataluna
Country [433] 0 0
Spain
State/province [433] 0 0
Catalunya
Country [434] 0 0
Spain
State/province [434] 0 0
Comunidad Valenciana
Country [435] 0 0
Spain
State/province [435] 0 0
Extremadura
Country [436] 0 0
Spain
State/province [436] 0 0
Galicia
Country [437] 0 0
Spain
State/province [437] 0 0
Girona
Country [438] 0 0
Spain
State/province [438] 0 0
Madrid
Country [439] 0 0
Spain
State/province [439] 0 0
Murcia
Country [440] 0 0
Spain
State/province [440] 0 0
Ciudad Real
Country [441] 0 0
Sweden
State/province [441] 0 0
Danderyd
Country [442] 0 0
Sweden
State/province [442] 0 0
Falun
Country [443] 0 0
Sweden
State/province [443] 0 0
Goteborg
Country [444] 0 0
Sweden
State/province [444] 0 0
Karlstad
Country [445] 0 0
Sweden
State/province [445] 0 0
Linkoping
Country [446] 0 0
Sweden
State/province [446] 0 0
Lund
Country [447] 0 0
Sweden
State/province [447] 0 0
Orebro
Country [448] 0 0
Sweden
State/province [448] 0 0
Stockholm
Country [449] 0 0
Sweden
State/province [449] 0 0
Vasteras
Country [450] 0 0
Switzerland
State/province [450] 0 0
Basel
Country [451] 0 0
Switzerland
State/province [451] 0 0
Bern
Country [452] 0 0
Switzerland
State/province [452] 0 0
Biel
Country [453] 0 0
Switzerland
State/province [453] 0 0
Lausanne
Country [454] 0 0
Switzerland
State/province [454] 0 0
Lugano
Country [455] 0 0
Switzerland
State/province [455] 0 0
Zurich
Country [456] 0 0
Taiwan
State/province [456] 0 0
Taiwan ROC
Country [457] 0 0
Taiwan
State/province [457] 0 0
Changhua
Country [458] 0 0
Taiwan
State/province [458] 0 0
Kaohsiung
Country [459] 0 0
Taiwan
State/province [459] 0 0
New Taipei
Country [460] 0 0
Taiwan
State/province [460] 0 0
Taichung
Country [461] 0 0
Taiwan
State/province [461] 0 0
Tainan
Country [462] 0 0
Taiwan
State/province [462] 0 0
Taipei
Country [463] 0 0
Taiwan
State/province [463] 0 0
Yilan
Country [464] 0 0
Turkey
State/province [464] 0 0
TUR
Country [465] 0 0
Turkey
State/province [465] 0 0
Ankara
Country [466] 0 0
Turkey
State/province [466] 0 0
Haydarpasa Istanbul
Country [467] 0 0
Turkey
State/province [467] 0 0