Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure With Reduced Ejection Fraction Suffering From Worsening Chronic Heart Failure (SOCRATES-REDUCED)

NCT01951625 | Completed Phase 2 Results DMC

• 2 other identifiers: 153712013-002287-11
• Study Type: interventional
• Target: 456
• Locations: 23 countries
• Sites: 152

Brief Summary

Objective of the study is to find the optimal dose of the once daily oral soluble guanylate cyclase stimulator (sGC) BAY1021189 for Phase III that can be given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).

Conditions

Heart Failure

Keywords

Worsening Heart Failure; Heart Failure with Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12

  Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.

  Baseline, Week 12

Other Outcomes (14)

• Changes in Heart Function as Measured by Echocardiography, Left Ventricular End-Diastolic Volume (LVEDV), and Left Ventricular End-Systolic Volume (LVESV) From Baseline to Week 12

  Baseline, Week 12

• Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12

  Baseline, Week 12

• Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12

  Baseline, Week 12

Study Arms (5)

Vericiguat (BAY1021189) (10 mg)

EXPERIMENTAL

2.5 mg orally once daily for 2 weeks, up-titration to 5 mg orally once daily for 2 weeks, up-titration to 10 mg orally once daily for 8 weeks

Drug: Vericiguat (BAY1021189) (1.25 mg); Drug: Vericiguat (BAY1021189) (5 mg)

Vericiguat (BAY1021189) (5 mg)

EXPERIMENTAL

2.5 mg orally once daily for 2 weeks, then 5 mg orally once daily for 10 weeks (with sham titration)

Drug: Vericiguat (BAY1021189) (1.25 mg); Drug: Vericiguat (BAY1021189) (5 mg)

Vericiguat (BAY1021189) (2.5 mg)

EXPERIMENTAL

2.5 mg orally once daily for 12 weeks (with sham titrations)

Drug: Vericiguat (BAY1021189) (1.25 mg)

Vericiguat (BAY1021189) (1.25 mg)

EXPERIMENTAL

1.25 mg orally once daily for 12 weeks (with sham titrations)

Drug: Vericiguat (BAY1021189) (1.25 mg)

Placebo

PLACEBO COMPARATOR

Orally once daily for 12 weeks (with sham titrations)

Drug: Placebo

Interventions

Vericiguat (BAY1021189) (1.25 mg) DRUG

1.25 mg BAY1021189 tablets

Vericiguat (BAY1021189) (1.25 mg); Vericiguat (BAY1021189) (10 mg); Vericiguat (BAY1021189) (2.5 mg); Vericiguat (BAY1021189) (5 mg)

Vericiguat (BAY1021189) (5 mg) DRUG

5 mg BAY1021189 tablets

Vericiguat (BAY1021189) (10 mg); Vericiguat (BAY1021189) (5 mg)

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Worsening chronic heart failure (WCHF) requiring hospitalization (or intravenous diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization
• Left ventricular ejection fraction (LVEF) \<45% by echocardiography at randomization

You may not qualify if:

• Intravenous inotropes at any time after hospitalization

Sponsors & Collaborators

• Bayer: lead

Study Sites (157)

Unknown Facility

Fountain Valley, California, 92708, United States

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Wilmington, Delaware, 19803, United States

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Fort Lauderdale, Florida, 33308, United States

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Jacksonville, Florida, 32209, United States

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Naples, Florida, 34102, United States

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Atlanta, Georgia, 30342, United States

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Macon, Georgia, 31201, United States

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New Orleans, Louisiana, 70112-1396, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55422, United States

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Jackson, Mississippi, 39216-4505, United States

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Buffalo, New York, 14215, United States

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Columbus, Ohio, 43210, United States

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Fairfield, Ohio, 45014, United States

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Charleston, South Carolina, 29425, United States

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Germantown, Tennessee, 38138, United States

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Nashville, Tennessee, 37232-8802, United States

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Milwaukee, Wisconsin, 53215, United States

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Darlinghurst, New South Wales, 2010, Australia

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Hobart, Tasmania, 7000, Australia

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Prahran, Victoria, 3181, Australia

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Sankt Pölten, Lower Austria, 3100, Austria

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Graz, Styria, 8036, Austria

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Linz, Upper Austria, 4020, Austria

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Salzburg, 5020, Austria

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Vienna, 1220, Austria

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Bruges, 8000, Belgium

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Bruxelles - Brussel, 1200, Belgium

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Ghent, 9000, Belgium

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Gilly, 6060, Belgium

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Huy, 4500, Belgium

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Mechelen, 2800, Belgium

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Mol, 2400, Belgium

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Roeselare, 8800, Belgium

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Sofia, 1202, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1309, Bulgaria

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Sofia, 1527, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Toronto, Ontario, M5B 1W8, Canada

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Montreal, Quebec, H1T 1C8, Canada

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Montreal, Quebec, H2W 1T8, Canada

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Saint-Jean-sur-Richelieu, Quebec, J3A 1C3, Canada

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Sherbrooke, Quebec, J1G 2E8, Canada

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Québec, G1V 4G5, Canada

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Hradec Králové, 500 05, Czechia

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Kroměříž, 767 01, Czechia

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Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

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Prague, 10034, Czechia

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Prague, 12808, Czechia

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Prague, 140 21, Czechia

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Prague, 169 02, Czechia

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Slaný, 274 01, Czechia

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Aalborg, 9000, Denmark

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Aarhus N, 8200, Denmark

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Hellerup, DK-2900, Denmark

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Viborg, 8800, Denmark

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Bron, 69677, France

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La Tronche, 38700, France

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Lille, 59037, France

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Paris, 75908, France

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Pessac, 33604, France

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Rouen, 76031, France

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München, Bavaria, 80331, Germany

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Bad Homburg, Hesse, 61348, Germany

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Frankfurt am Main, Hesse, 60596, Germany

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Hanover, Lower Saxony, 30625, Germany

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Greifswald, Mecklenburg-Vorpommern, 17475, Germany

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Cologne, North Rhine-Westphalia, 50924, Germany

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Münster, North Rhine-Westphalia, 48149, Germany

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Homburg, Saarland, 66424, Germany

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Erfurt, Thuringia, 99089, Germany

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Hamburg, 20246, Germany

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Athens, 11527, Greece

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Nea Ionia, 14233, Greece

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Budapest, 1032, Hungary

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Kistarcsa, H-2143, Hungary

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Székesfehérvár, 8000, Hungary

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Afula, 1834111, Israel

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Ashkelon, 7830604, Israel

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Hadera, 3810101, Israel

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Jerusalem, 9103102, Israel

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Petah Tikva, 4941492, Israel

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Rehovot, 7610001, Israel

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Tel Aviv, 6423906, Israel

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Tiberias, 1528001, Israel

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Zrifin, 7030000, Israel

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Bergamo, Lombardy, 24127, Italy

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Brescia, Lombardy, 25123, Italy

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Como, Lombardy, 22020, Italy

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Milan, Lombardy, 20017, Italy

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Milan, Lombardy, 20138, Italy

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Milan, Lombardy, 20149, Italy

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Pavia, Lombardy, 27100, Italy

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Ancona, The Marches, 60126, Italy

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Arezzo, Tuscany, 52040, Italy

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Verona, Veneto, 37045, Italy

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Iizuka, Fukuoka, 820-8505, Japan

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Himeji, Hyōgo, 670-0981, Japan

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Kanazawa, Ishikawa-ken, 920-8650, Japan

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Sagamihara, Kanagawa, 252-5188, Japan

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Yokohama, Kanagawa, 236-0051, Japan

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Yokosuka, Kanagawa, 238-8567, Japan

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Sendai, Miyagi, 981-3133, Japan

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Naha, Okinawa, 902-8511, Japan

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Takatsuki, Osaka, 569-1096, Japan

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Yao, Osaka, 581-0011, Japan

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Ureshino, Saga-ken, 843-0393, Japan

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Komatsushimachō, Tokushima, 773-8502, Japan

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Meguro-ku, Tokyo, 152-8902, Japan

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Minato-ku, Tokyo, 106-0031, Japan

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Fukui, 910-8526, Japan

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Hiroshima, 734-8530, Japan

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Kumamoto, 862-8505, Japan

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Nagasaki, 850-8555, Japan

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Tokushima, 770-8539, Japan

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Toyama, 930-8550, Japan

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Amsterdam, 1105 AZ, Netherlands

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Deventer, 7416 SE, Netherlands

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Heerenveen, 8441 PW, Netherlands

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Leeuwarden, 8901 BR, Netherlands

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Veldhoven, 5504 DB, Netherlands

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Bialystok, 15-276, Poland

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Krakow, 31-202, Poland

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Legnica, 59-220, Poland

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Lodz, 92-213, Poland

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Olsztyn, 10-010, Poland

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Poznan, 61-848, Poland

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Warsaw, 02-507, Poland

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Singapore, 119228, Singapore

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Singapore, 169609, Singapore

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Singapore, 308433, Singapore

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Singapore, 768828, Singapore

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Seoul, 138-736, South Korea

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Santander, Cantabria, 39008, Spain

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Majadahonda, Madrid, 28222, Spain

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Barcelona, 08003, Spain

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Barcelona, 08023, Spain

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Valencia, 46010, Spain

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Valencia, 46026, Spain

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Helsingborg, 251 87, Sweden

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Karlstad, 651 85, Sweden

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Linköping, 581 85, Sweden

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Malmo, 205 02, Sweden

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Örebro, 701 85, Sweden

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Stockholm, 118 83, Sweden

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Liestal, Basel-Landschaft, 4410, Switzerland

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Bruderholz, 4101, Switzerland

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Lugano, 6900, Switzerland

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Zurich, 8091, Switzerland

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Kaohsiung City, 813, Taiwan

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New Taipei City, 220, Taiwan

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Taipei, 10016, Taiwan

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Taipei, 11217, Taiwan

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Chesterfield, Derbyshire, S44 5DX, United Kingdom

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Stevenage, Hertfordshire, SG1 4AB, United Kingdom

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Related Publications (4)

• Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Muller K, Roessig L, Gheorghiade M; SOCRATES Investigators and Coordinators. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail. 2014 Sep;16(9):1026-38. doi: 10.1002/ejhf.135. Epub 2014 Jul 24.

  PMID: 25056511 RESULT

• Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Muller K, Roessig L, Pieske B; SOCRATES-REDUCED Investigators and Coordinators. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. JAMA. 2015 Dec 1;314(21):2251-62. doi: 10.1001/jama.2015.15734.

  PMID: 26547357 RESULT

• Ruehs H, Klein D, Frei M, Grevel J, Austin R, Becker C, Roessig L, Pieske B, Garmann D, Meyer M. Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. Clin Pharmacokinet. 2021 Nov;60(11):1407-1421. doi: 10.1007/s40262-021-01024-y. Epub 2021 Jun 4.

  PMID: 34086190 DERIVED

• Kramer F, Voss S, Roessig L, Igl BW, Butler J, Lam CSP, Maggioni AP, Shah SJ, Pieske B. Evaluation of high-sensitivity C-reactive protein and uric acid in vericiguat-treated patients with heart failure with reduced ejection fraction. Eur J Heart Fail. 2020 Sep;22(9):1675-1683. doi: 10.1002/ejhf.1787. Epub 2020 Mar 25.

  PMID: 32216011 DERIVED

Related Links

• Click here to find results for studies related to Bayer Healthcare products.

MeSH Terms

Conditions

Heart Failure

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Endpoints of "Change in 'health-related quality of life', 'Composite Congestion Score', 'NYHA function class', and 'background heart failure therapies' were assessed as exploratory. "Incidence of atrial fibrillation" is reported in AE summary.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: September 26, 2013
• Study Start: November 29, 2013
• Primary Completion: May 14, 2015
• Study Completion: June 9, 2015
• Last Updated: March 25, 2021
• Results First Posted: March 25, 2021

Record last verified: 2021-03

Locations

US (18); PL (7); NL (5); GR (2); IT (10); ES (7); TW (4); DK (4); SG (4); IL (9); SE (6); FR (6); DE (10); BU (5); BE (8); HU (3); AU (3); CZ (8); JP (20); KR (1); CH (4); CA (6); GB (2)