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A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure
NCT06742723 · AstraZeneca
In plain English
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Official title
A Phase III, Randomised, Double-blind, Placebo-controlled, Event-driven Study to Assess the Efficacy, Safety and Tolerability of Baxdrostat in Combination With Dapagliflozin Compared With Dapagliflozin Alone on Renal Outcomes and Cardiovascular Mortality in Participants With Chronic Kidney Disease and High Blood Pressure
About this study
The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite endpoint of ≥ 50% sustained decline in eGFR, kidney failure, HF events, or CV death in participants with CKD and HTN.
This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin.
Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months.
The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred (N = 845) ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within 6 weeks of the PACD. This period can be extended by AstraZeneca.
In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. Baxdrostat/placebo should not be administered without dapagliflozin: baxdrostat/placebo should be interrupted if dapagliflozin is interrupted (baxdrostat/placebo may be resumed with dapagliflozin, if dapagliflozin is resumed), and should be permanently discontinued if dapagliflozin is permanently discontinued. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.
Eligibility criteria
Inclusion Criteria:
1. Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent.
2. Participants with (a) or (b):
a) eGFR 30-59 mL/min/1.73 m² (local or central laboratory value) AND:
* UACR ≥ 30 mg/g (3.39 mg/mmol) and \< 500 mg/g (56.5 mg/mmol) (central laboratory value only), or
* UACR ≥ 500 mg/g (56.5 mg/mmol) and ≤ 5000 mg/g (565 mg/mmol) (local or central laboratory value), or
* UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local laboratory value only).
(b) eGFR 60-75 mL/min/1.73 m² (local or central laboratory value) AND:
* UACR ≥ 500 mg/g (56.5 mg/mmol) ) and ≤ 5000 mg/g (565 mg/mmol) (local or central laboratory value), or
* UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local laboratory value only)
3. \[obsolete\]
4. Participants with history of HTN and a SBP ≥ 130 mmHg (the most recent value within 4 weeks prior to screening or at the Screening Visit) and ≥ 120 mmHg at the Randomisation Visit.
5. Stable and maximum tolerated dose of an ACEi or an ARB (not both) for at least 4 weeks prior to Screening Visit.
6. Participants with:
1. Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2 (local or central laboratory values)
2. Serum or plasma potassium ≥ 3.0 and ≤ 4.5 mmol/L if eGFR \< 45 mL/min/1.73 m2 (local or central laboratory values)
Exclusion Criteria:
1. Systolic blood pressure \> 180 mmHg, or diastolic BP \> 110 mmHg at screening.
2. Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening.
3. Serum sodium \< 135 mmol/L (central or local laboratory values obtained within 4 weeks prior to screening or at the Screening Visit).
4\. Participants with T1DM will be excluded, except:
1. For US only: patients with T1DM treated with SGLT2i for at least 4 months, without DKA during that period, and who have experience with ketone monitoring are eligible for inclusion.
2. For Japan only: patients with T1DM treated with dapagliflozin 10 mg for at least 4 months, without DKA during the period of dapagliflozin treatment are eligible for inclusion.
5 Uncontrolled T2DM with HbA1c \> 10.5% (\> 91 mmol/mol) (central or local laboratory values obtained within 3 months prior to screening or at the Screening Visit).
6 New York Heart Association functional HF class IV at screening.
7 Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening heart failure within previous 3 months prior to randomisation.
8 Documented history of adrenal insufficiency.
9 Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.
10 Any acute kidney injury within 3 months prior to the Screening Visit.
11 History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
12 Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months prior to Visit 1).
Study design
Enrollment target: 5000 participants
Allocation: randomized
Masking: quadruple
Age groups: adult, older_adult
Timeline
Starts: 2025-03-03
Estimated completion: 2029-12-18
Last updated: 2026-03-27
Interventions
Drug: Baxdrostat/dapagliflozinDrug: Placebo/dapagliflozin
Primary outcomes
- • To determine if baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of ≥ 50% sustained decline in eGFR, kidney failure, Heart Failure events(HF), or CV death. (Up to 37 months)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
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Vijayawada, India
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Vijayawada, India
Research SiteRecruiting
Afula, Israel
Research SiteRecruiting
Ashdod, Israel
Research SiteRecruiting
Be’er Ya‘aqov, Israel
Research SiteRecruiting
Haifa, Israel
Research SiteRecruiting
Haifa, Israel
Research SiteWithdrawn
Jerusalem, Israel
Research SiteRecruiting
Kfar Saba, Israel
Research SiteRecruiting
Nahariya, Israel
Research SiteRecruiting
Petah Tikva, Israel
Research SiteRecruiting
Rehovot, Israel
Research SiteRecruiting
Tel Aviv, Israel
Research SiteRecruiting
Bassano del Grappa, Italy
Research SiteRecruiting
Bologna, Italy
Research SiteRecruiting
Desio, Italy
Research SiteRecruiting
Foggia, Italy
Research SiteRecruiting
Genoa, Italy
Research SiteRecruiting
Modena, Italy
Research SiteRecruiting
Naples, Italy
Research SiteRecruiting
Novara, Italy
Research SiteRecruiting
Padova, Italy
Research SiteRecruiting
Pavia, Italy
Research SiteRecruiting
Pisa, Italy
Research SiteRecruiting
Pordenone, Italy
Research SiteRecruiting
Roma, Italy
Research SiteRecruiting
Rozzano, Italy
Research SiteRecruiting
Torino, Italy
Research SiteRecruiting
Tradate, Italy
Research SiteRecruiting
Aira, Japan
Research SiteRecruiting
Amagasaki-shi, Japan
Research SiteRecruiting
Beppu-shi, Japan
Research SiteRecruiting
Chigasaki-shi, Japan
Research SiteWithdrawn
Fujinomiya-shi, Japan
Research SiteRecruiting
Hakodate-shi, Japan
Research SiteRecruiting
Hamamatsu, Japan
Research SiteRecruiting
Higashihiroshima-shi, Japan
Research SiteRecruiting
Iizuka-shi, Japan
Research SiteRecruiting
Inashiki-gun, Japan
Research SiteRecruiting
Itabashi-ku, Japan
Research SiteRecruiting
Iwata-shi, Japan
Research SiteRecruiting
Kagoshima, Japan
Research SiteRecruiting
Kamakura-shi, Japan
Research SiteRecruiting
Kanazawa, Japan
Research SiteRecruiting
Kashiwara-shi, Japan
Research SiteRecruiting
Kasugai-shi, Japan
Research SiteRecruiting
Kita-ku, Japan
Research SiteRecruiting
Kitakyushu, Japan
Research SiteRecruiting
Kitakyushu-shi, Japan
Research SiteRecruiting
Kobe, Japan
Research SiteWithdrawn
Kobe, Japan
Research SiteRecruiting
Kumagaya-shi, Japan
Research SiteRecruiting
Kurashiki Shi, Japan
Research SiteRecruiting
Kuse-gun, Japan
Research SiteRecruiting
Kuwana-shi, Japan
Research SiteRecruiting
Kyoto, Japan
Research SiteRecruiting
Kyoto, Japan
Research SiteRecruiting
Matsusaka-shi, Japan
Research SiteRecruiting
Matsuyama, Japan
Research SiteRecruiting
Matsuyama, Japan
Research SiteRecruiting
Meguro-ku, Japan
Research SiteRecruiting
Minatoku, Japan
Research SiteRecruiting
Minatoku, Japan
Research SiteRecruiting
Minokamo Shi, Japan
Research SiteRecruiting
Miyakonojo-shi, Japan
Research SiteRecruiting
Morioka, Japan
Research SiteRecruiting
Nagaoka-shi, Japan
Research SiteRecruiting
Naka, Japan
Research SiteRecruiting
Narita-shi, Japan
Research SiteRecruiting
Obihiro-shi, Japan
Research SiteWithdrawn
Osaka, Japan
Research SiteRecruiting
Osaka, Japan
Research SiteRecruiting
Osaka, Japan
Research SiteRecruiting
Osaka, Japan
Research SiteRecruiting
Osaka, Japan
Research SiteRecruiting
Ōita, Japan
Research SiteRecruiting
Ōme, Japan
Research SiteRecruiting
Ōmihachiman, Japan
Research SiteRecruiting
Saga, Japan
Research SiteRecruiting
Sapporo, Japan
Research SiteRecruiting
Sapporo, Japan
Research SiteRecruiting
Sapporo, Japan
Research SiteRecruiting
Sendai, Japan
Research SiteRecruiting
Sendai, Japan
Research SiteRecruiting
Shibuya-ku, Japan
Research SiteRecruiting
Tanabe-shi, Japan
Research SiteRecruiting
Toyoake-shi, Japan
Research SiteRecruiting
Toyohashi, Japan
Research SiteRecruiting
Tsu, Japan
Research SiteRecruiting
Yaizu-shi, Japan
Research SiteRecruiting
Yokohama, Japan
Research SiteRecruiting
Yoshida-gun, Japan
Research SiteRecruiting
Ampang, Malaysia
Research SiteRecruiting
Cheras, Malaysia
Research SiteRecruiting
Ipoh, Malaysia
Research SiteRecruiting
Kajang, Malaysia
Research SiteRecruiting
Kota Bharu, Malaysia
Research SiteRecruiting
Kuala Lumpur, Malaysia
Research SiteRecruiting
Seremban, Malaysia
Research SiteRecruiting
Seri Manjung, Malaysia
Research SiteRecruiting
Chihuahua City, Mexico
Research SiteNot Yet Recruiting
Cuauhtémoc, Mexico
Research SiteRecruiting
Cuauhtémoc, Mexico
Research SiteRecruiting
D.F, Mexico
Research SiteRecruiting
Durango, Mexico
Research SiteRecruiting
Guadalajara, Mexico
Research SiteRecruiting
Guadalajara, Mexico
Research SiteRecruiting
Mazatlán, Mexico
Research SiteRecruiting
Mazatlán, Mexico
Research SiteRecruiting
Mérida, Mexico
Research SiteRecruiting
San Luis Potosí City, Mexico
Research SiteRecruiting
Veracruz, Mexico
Research SiteRecruiting
Zapopan, Mexico
Research SiteRecruiting
Amersfoort, Netherlands
Research SiteRecruiting
Amsterdam, Netherlands
Research SiteRecruiting
Dordrecht, Netherlands
Research SiteRecruiting
Groningen, Netherlands
Research SiteRecruiting
Hilversum, Netherlands
Research SiteRecruiting
Leiden, Netherlands
Research SiteRecruiting
Maastricht, Netherlands
Research SiteRecruiting
Nieuwegein, Netherlands
Research SiteRecruiting
Zwolle, Netherlands
Research SiteSuspended
Arequipa, Peru
Research SiteNot Yet Recruiting
Bellavista, Peru
Research SiteRecruiting
Chorrillos, Peru
Research SiteNot Yet Recruiting
Cusco, Peru
Research SiteRecruiting
Lima, Peru
Research SiteRecruiting
Lima, Peru
Research SiteNot Yet Recruiting
Lima, Peru
Research SiteWithdrawn
Lima, Peru
Research SiteRecruiting
Lima, Peru
Research SiteRecruiting
Lima, Peru
Research SiteRecruiting
Piura, Peru
Research SiteRecruiting
Cebu City, Philippines
Research SiteNot Yet Recruiting
Davao City, Philippines
Research SiteRecruiting
Davao City, Philippines
Research SiteRecruiting
Iloilo City, Philippines
Research SiteRecruiting
Laguna, Philippines
Research SiteNot Yet Recruiting
Manadaluyong City, Philippines
Research SiteNot Yet Recruiting
Manila, Philippines
Research SiteRecruiting
Quezon City, Philippines
Research SiteWithdrawn
Quezon City, Philippines
Research SiteWithdrawn
San Fernando City, Philippines
Research SiteRecruiting
Bialystok, Poland
Research SiteRecruiting
Gdynia, Poland
Research SiteRecruiting
Gdynia, Poland
Research SiteRecruiting
Gmina Świecie, Poland
Research SiteSuspended
Jasło, Poland
Research SiteRecruiting
Katowice, Poland
Research SiteRecruiting
Katowice, Poland
Research SiteRecruiting
Katowice, Poland
Research SiteRecruiting
Krakow, Poland
Research SiteSuspended
Krakow, Poland
Research SiteRecruiting
Krakow, Poland
Research SiteRecruiting
Krakow, Poland
Research SiteRecruiting
Krakow, Poland
Research SiteRecruiting
Lodz, Poland
Research SiteRecruiting
Lodz, Poland
Research SiteRecruiting
Lublin, Poland
Research SiteWithdrawn
Piaseczno, Poland
Research SiteRecruiting
Poznan, Poland
Research SiteNot Yet Recruiting
Poznan, Poland
Research SiteRecruiting
Poznan, Poland
Research SiteRecruiting
Pruszków, Poland
Research SiteRecruiting
Radom, Poland
Research SiteRecruiting
Rzeszów, Poland
Research SiteRecruiting
Szczecin, Poland
Research SiteRecruiting
Szczecin, Poland
Research SiteRecruiting
Szczecin, Poland
Research SiteRecruiting
Tczew, Poland
Research SiteRecruiting
Warsaw, Poland
Research SiteNot Yet Recruiting
Warsaw, Poland
Research SiteRecruiting
Warsaw, Poland
Research SiteRecruiting
Warsaw, Poland
Research SiteRecruiting
Warsaw, Poland
Research SiteRecruiting
Warsaw, Poland
Research SiteRecruiting
Warsaw, Poland
Research SiteRecruiting
Wroclaw, Poland
Research SiteRecruiting
Wroclaw, Poland
Research SiteRecruiting
Żywiec, Poland
Research SiteWithdrawn
Brasov, Romania
Research SiteRecruiting
Bucharest, Romania
Research SiteRecruiting
Bucharest, Romania
Research SiteSuspended
Bucharest, Romania
Research SiteRecruiting
Bucharest, Romania
Research SiteNot Yet Recruiting
Bucharest, Romania
Research SiteRecruiting
Cluj-Napoca, Romania
Research SiteRecruiting
Craiova, Romania
Research SiteRecruiting
Craiova, Romania
Research SiteRecruiting
Oradea, Romania
Research SiteRecruiting
Suceava, Romania
Research SiteRecruiting
Timișoara, Romania
Research SiteRecruiting
Al-Ahsa, Saudi Arabia
Research SiteRecruiting
Dammam, Saudi Arabia
Research SiteWithdrawn
Riyadh, Saudi Arabia
Research SiteRecruiting
Riyadh, Saudi Arabia
Research SiteRecruiting
Riyadh, Saudi Arabia
Research SiteNot Yet Recruiting
Riyadh, Saudi Arabia
Research SiteRecruiting
Riyadh/MENA, Saudi Arabia
Research SiteRecruiting
Belgrade, Serbia
Research SiteWithdrawn
Belgrade, Serbia
Research SiteNot Yet Recruiting
Belgrade, Serbia
Research SiteNot Yet Recruiting
Belgrade, Serbia
Research SiteWithdrawn
Belgrade, Serbia
Research SiteNot Yet Recruiting
Kamenitz, Serbia
Research SiteRecruiting
Kragujevac, Serbia
Research SiteWithdrawn
Kragujevac, Serbia
Research SiteRecruiting
Niš, Serbia
Research SiteWithdrawn
Novi Sad, Serbia
Research SiteRecruiting
Novi Sad, Serbia
Research SiteRecruiting
Singapore, Singapore
Research SiteRecruiting
Singapore, Singapore
Research SiteRecruiting
Singapore, Singapore
Research SiteRecruiting
Singapore, Singapore
Research SiteRecruiting
Košice, Slovakia
Research SiteWithdrawn
Kráľovský Chlmec, Slovakia
Research SiteRecruiting
Myjava, Slovakia
Research SiteRecruiting
Nitra, Slovakia
Research SiteRecruiting
Prešov, Slovakia
Research SiteWithdrawn
Prešov, Slovakia
Research SiteRecruiting
Púchov, Slovakia
Research SiteRecruiting
Trenčín, Slovakia
Research SiteRecruiting
Trnava, Slovakia
Research SiteRecruiting
Žilina, Slovakia
Research SiteRecruiting
Bellville, South Africa
Research SiteRecruiting
Benoni, South Africa
Research SiteWithdrawn
Bloemfontein, South Africa
Research SiteRecruiting
Bloemfontein, South Africa
Research SiteRecruiting
Cape Town, South Africa
Research SiteRecruiting
Cape Town, South Africa
Research SiteRecruiting
Durban, South Africa
Research SiteWithdrawn
Durban, South Africa
Research SiteWithdrawn
Durban, South Africa
Research SiteRecruiting
Extension 8, Lenasia, South Africa
Research SiteRecruiting
KwaDukuza, South Africa
Research SiteRecruiting
Lenasia, South Africa
Research SiteRecruiting
Midrand, South Africa
Research SiteRecruiting
Newton, South Africa
Research SiteWithdrawn
Parow, South Africa
Research SiteRecruiting
Ansan-si, South Korea
Research SiteRecruiting
Anyang-si, South Korea
Research SiteRecruiting
Busan, South Korea
Research SiteRecruiting
Cheonan-si, South Korea
Research SiteRecruiting
Goyang-si, South Korea
Research SiteRecruiting
Gwangju, South Korea
Research SiteRecruiting
Seongnam-si, South Korea
Research SiteRecruiting
Seoul, South Korea
Research SiteRecruiting
Seoul, South Korea
Research SiteRecruiting
Seoul, South Korea
Research SiteRecruiting
Wŏnju, South Korea
Research SiteRecruiting
Yangsan, South Korea
Research SiteRecruiting
A Coruña, Spain
Research SiteRecruiting
Almería, Spain
Research SiteRecruiting
Badalona, Spain
Research SiteRecruiting
L'Hospitalet de Llobregat, Spain
Research SiteRecruiting
Majadahonda, Spain
Research SiteRecruiting
Málaga, Spain
Research SiteSuspended
Palma deMallorca, Spain
Research SiteRecruiting
Pamplona, Spain
Research SiteRecruiting
Seville, Spain
Research SiteRecruiting
Seville, Spain
Research SiteRecruiting
Valencia, Spain
Research SiteRecruiting
Valencia, Spain
Research SiteRecruiting
Huddinge, Sweden
Research SiteRecruiting
Karlstad, Sweden
Research SiteRecruiting
Linköping, Sweden
Research SiteRecruiting
Stockholm, Sweden
Research SiteRecruiting
Uppsala, Sweden
Research SiteRecruiting
Vaxjo, Sweden
Research SiteRecruiting
New Taipei City, Taiwan
Research SiteRecruiting
Taichung, Taiwan
Research SiteRecruiting
Taichung, Taiwan
Research SiteRecruiting
Taipei, Taiwan
Research SiteRecruiting
Taipei, Taiwan
Research SiteRecruiting
Taipei, Taiwan
Research SiteRecruiting
Taoyuan District, Taiwan
Research SiteRecruiting
Yung Kang City, Taiwan
Research SiteRecruiting
Bangkok, Thailand
Research SiteRecruiting
Bangkok, Thailand
Research SiteRecruiting
Bangkok, Thailand
Research SiteRecruiting
Banphaeo, Thailand
Research SiteRecruiting
Hat Yai, Thailand
Research SiteRecruiting
Khon Kaen, Thailand
Research SiteRecruiting
Mueang, Thailand
Research SiteRecruiting
Phutthamonthon, Thailand
Research SiteRecruiting
Ubonratchathani, Thailand
Research SiteRecruiting
Adana, Turkey (Türkiye)
Research SiteRecruiting
Adapazarı, Turkey (Türkiye)
Research SiteRecruiting
Altındağ, Turkey (Türkiye)
Research SiteRecruiting
Ankara, Turkey (Türkiye)
Research SiteRecruiting
Antalya, Turkey (Türkiye)
Research SiteRecruiting
Haliliye, Turkey (Türkiye)
Research SiteRecruiting
Kahramanmaraş, Turkey (Türkiye)
Research SiteRecruiting
Kayseri, Turkey (Türkiye)
Research SiteRecruiting
Kocaeli, Turkey (Türkiye)
Research SiteRecruiting
Şahinbey, Turkey (Türkiye)
Research SiteRecruiting
Chernivtsі, Ukraine
Research SiteRecruiting
Ivano-Frankivsk, Ukraine
Research SiteRecruiting
Kyiv, Ukraine
Research SiteRecruiting
Kyiv, Ukraine
Research SiteRecruiting
Kyiv, Ukraine
Research SiteRecruiting
Kyiv, Ukraine
Research SiteRecruiting
Kyiv, Ukraine
Research SiteRecruiting
Ternopil, Ukraine
Research SiteRecruiting
Ternopil, Ukraine
Research SiteRecruiting
Uzhhorod, Ukraine
Research SiteRecruiting
Uzhhorod, Ukraine
Research SiteRecruiting
Vinnytsia, Ukraine
Research SiteRecruiting
Vinnytsia, Ukraine
Research SiteRecruiting
Vinnytsia, Ukraine
Research SiteTerminated
Zhytomyr, Ukraine
Research SiteRecruiting
Bradford, United Kingdom
Research SiteRecruiting
Bristol, United Kingdom
Research SiteRecruiting
Canterbury, United Kingdom
Research SiteRecruiting
Cardiff, United Kingdom
Research SiteRecruiting
Dundee, United Kingdom
Research SiteRecruiting
Glasgow, United Kingdom
Research SiteRecruiting
Hounslow, United Kingdom
Research SiteRecruiting
London, United Kingdom
Research SiteRecruiting
London, United Kingdom
Research SiteRecruiting
Salford, United Kingdom
Research SiteWithdrawn
Southampton, United Kingdom
Research SiteRecruiting
Swansea, United Kingdom
Research SiteRecruiting
Da Nang, Vietnam
Research SiteRecruiting
Haiphong, Vietnam
Research SiteRecruiting
Hanoi, Vietnam
Research SiteRecruiting
Ho Chi Minh City, Vietnam
Research SiteWithdrawn
Ho Chi Minh City, Vietnam
Research SiteNot Yet Recruiting
Ho Chi Minh City, Vietnam
Research SiteRecruiting
Ho Chi Minh City, Vietnam
Research SiteNot Yet Recruiting
Rach Gia, Vietnam