Phase III Trial of Dantonic® (T89) Capsule to Prevent and Treat Stable Angina (CAESA)

Phase III Confirmatory Trial to Confirm the Anti-anginal Effect of Dantonic® (T89) in Patients With Chronic Stable Angina

This phase III study is designed as a double blind, randomized, multi-nation, multi-center, placebo controlled clinical research, which aims to evaluate the safety and efficacy of Dantonic® (T89) in patients with chronic stable angina pectoris.

Study Overview

• Status: Completed
• Conditions: Angina Pectoris
• Intervention / Treatment: Drug: T89 high dose; Drug: T89 Low dose; Drug: Sanqi+Bingpian; Drug: Placebo

Detailed Description

Dantonic® (T89) is a botanical drug consists of extracts of Danshen (Radix Salviae Miltiorrhizae) and Sanqi (Radix Notoginseng) with borneol in a capsule form. The drug is currently approved in 26 countries outside the USA for the treatment and prevention of chronic stable angina pectoris and other cardiovascular disease related conditions. This pivotal confirmative Phase III clinical trial is to confirm the efficacy and safety of the drug at 150mg and 225mg doses in the prevention and treatment of angina pectoris in patients with Chronic Stable Angina. The contribution of the main herb Danshen to, and the difference of various production batches in, the overall efficacy and safety profiles will also be explored. Patients will take a morning and an evening dose orally (every 12 hours) for 6 weeks while stop taking any long-acting nitroglycerin, ranolazine, and/or multiple beta-blockers or beta blocker(s) with calcium channel blocker during the trial. Single beta-blocker and/or on-demand short acting nitroglycerin to relief angina pectoris is allowed during the trial. After physical exams and if eligible to participation, patients will stop taking other drugs, and undergo two baseline screen Exercise Treadmill Tests (ETT) on Standard Bruce Protocol in the clinic one week before and right before starting the drug treatment. Patients will perform three more ETTs before the morning dose at the end of week 2, 4 and 6 after receiving the drug treatment. The primary efficiency endpoint is the change of symptom-limited Total Exercise Duration of the ETT at the end of the 4th week of treatment from the average of the two screening baselines compared with that of placebo treatment.

• Study Type: Interventional
• Enrollment (Actual): 1004
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 223041
    • Minsk Regional Clinical Hospital
• Canada
  • Quebec, Canada, G1V 4G5
    • Institut universitaire de Cardiologie et de Pneumologie de Quebec
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1V6
      • Dr. Petr Polasek, MD, Office of
    • North Vancouver, British Columbia, Canada, V7L 2P7
      • The Medical Arts Health Research Group
    • Victoria, British Columbia, Canada, V8R 4R2
      • Victoria Heart Institute Foundation
  • Ontario
    • Mississauga, Ontario, Canada, L4W 0C2
      • Dixie Medical Group
    • Oshawa, Ontario, Canada, L1J 2J9
      • Heart Care Research
    • Oshawa, Ontario, Canada, L1H 1B9
      • Bakbak Medicine Professional Corporation
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Brossard, Quebec, Canada, J4X 1S4
      • Viacar Recherche Clinique Inc.
    • Greenfield Park, Quebec, Canada, J4V 2G8
      • Viacar Recherche Clinique Inc.
    • Longueuil, Quebec, Canada, J4M 2X1
      • Centre Cardiovasculaire De La Rive-Sud (Ccrs)
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Montreal, Quebec, Canada, H1T 3Y7
      • Clinique Sante Cardio MC
    • Trois-Rivieres, Quebec, Canada, G8Z 3R9
      • Centre de santé et de services sociaux de Trois-Rivières
• Georgia
  • Batumi, Georgia, 6000
    • The "Unimed Ajara"
  • Tbilisi, Georgia, 0144
    • Cardiological CLinic "Guli" Ltd
  • Tbilisi, Georgia, 0159
    • Archangel St. Michael Multiprofile Clinical Hospital
  • Tbilisi, Georgia, 0159
    • Cardio-Reanimation Centre
  • Tbilisi, Georgia, 0159
    • Emergency Cardiology Center named by Academician G. Chapidze Ltd
  • Tbilisi, Georgia, 0159
    • Tbilis Heart and vascular clinic Ltd.
  • Tbilisi, Georgia, 0160
    • Center of Vascular and Heart Diseases Ltd.
  • Tbilisi, Georgia, 4600
    • "Clinic L J" Ltd
• Mexico
  • Aguascalientes, Mexico, 20230
    • Hospital de Cardiología de Aguascalientes
  • Oaxaca, Mexico, 68000
    • OSMO
  • Baja California
    • Tijuana, Baja California, Mexico, 22010
      • Consultorio Medico de Especialidad
  • Coahuila
    • Torreón, Coahuila, Mexico, 27000
      • Centro para el Desarrollo de la Medicina y Asistencia Médica Especializada SC sede Torreon Coahuila
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Cardiocen de Guadalajara, S.C.
  • Michoacán
    • Morelia, Michoacán, Mexico, 58260
      • Centro de Investigación Clinica Chapultepec
  • SLP
    • San Luis Potosí, SLP, Mexico, 78240
      • Hospital Central "Dr. Ignacio Morones Prieto"
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, 80020
      • Centro para el Desarollo de la Medicina y de Asistencia Medica Esp. S.C.
• Russian Federation
  • Ekaterinburg, Russian Federation, 620036
    • Ural Medical Academy
  • Kemerovo, Russian Federation, 650055
    • Nonstate Healthcare Institution "Departmental Clinical Hospital on Kemerovo Station of Public Corporation "Russian Railroad"
  • Krasnodar, Russian Federation, 350086
    • Krasnodar regional hospital #1 n.a. Prof. Ochapovskiy S.V.
  • Moscow, Russian Federation, 111539
    • Moscow State Healthcare Institution, City Clinical Hospital #15
  • Moscow, Russian Federation, 119991
    • First Moscow State Medical University
  • Saint-Petersburg, Russian Federation, 197341
    • Almazov Federal Heart, Blood and Endocrinology Centre
  • St. Petersburg, Russian Federation, 192288
    • City Polyclinic # 109
  • St. Petersburg, Russian Federation, 196601
    • City Hospital #38 named after Semashko N.A.
  • St. Petersburg, Russian Federation, 197341
    • Almazov Federal Heart, Blood and Endocrinology Centre
  • St. Petersburg, Russian Federation, 199106
    • St. Petersburg State Health Care, Institution Pokrovskaya City Hospital
  • Tyumen, Russian Federation, 625026
    • Tyumen Cardiology Center
  • Vladimir, Russian Federation, 600020
    • City Hospital #4
  • Yaroslavl, Russian Federation, 150003
    • Clinical Hospital n.a. N.V. Solovyov
  • Ivanovslaya Obl.
    • Ivanovslaya, Ivanovslaya Obl., Russian Federation, 153012
      • Regional Buegetary Healthcare Institution "Cardiological Dispensary"
  • Russia
    • Novosibirsk, Russia, Russian Federation, 630087
      • State Budgetary Healthcare Institution "State Novosibirsk Regional Clinical Hospital"
    • Volgograd, Russia, Russian Federation, 400008
      • Regional cardiology center
  • Smoleskaya oblast
    • Smolensk, Smoleskaya oblast, Russian Federation, 214019
      • Smolensk State Medical Academy of RosZdrav
  • Tomskaya Obl.
    • Tomsk, Tomskaya Obl., Russian Federation, 634012
      • Federal State Budgetary Institution Research Institution Of Cardiology Of Sibirsky
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Regional Clinical Cardiology Dispensary, department of anesthesiology with intensive care unit
  • Kharkiv, Ukraine, 61039
    • L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine, Head of Cardiopulmonology Department Government Institution
  • Kharkiv, Ukraine, 61039
    • L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine
  • Kiev, Ukraine, 04114
    • Institute Of Gerontology, Department Of Clinical Physiology And Pathology Of Internal Organs
  • Kiev, Ukraine, 1601
    • Kyiv Oleksandrivska Clinical Hospital
  • Kiev, Ukraine, 2091
    • Municipal clinical hospital #1
  • Kiev, Ukraine, 4050
    • National medical university named after O.O.Bogomolets
  • Lviv, Ukraine, 79015
    • Lviv Regional State Clinical Threatment-and-Diagnostic Cardiology Center
  • Odessa, Ukraine, 65010
    • Department of Family Medicine and General Practice of Odessa National Medical University
  • Odessa, Ukraine, 65014
    • City Clinical Hospital No. 3
  • Odessa, Ukraine, 65025
    • Odessa regional cardiological dispensary
  • Uzhgorod, Ukraine, 88000
    • District Clinical Hospital Of Station "Uzhgorod", Dgto "Lviv Railway Station" Therapeutic Department
  • Vinnitsa, Ukraine, 21029
    • City Clinical Hospital # 1
  • Vinnytsya, Ukraine, 21018
    • Vinnytsya Regional Specialized Center for Radiation Protection of People
  • Zaporizhzhya region
    • Zaporizhzhya, Zaporizhzhya region, Ukraine, 69005
      • Regional medical center of cardiovascular diseases
    • Zaporizhzhya, Zaporizhzhya region, Ukraine, 69118
      • Department of internal diseases #2
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Cardiology and Medicine Clinic
  • California
    • Banning, California, United States, 92220
      • Beaver Medical Clinic
    • La Jolla, California, United States, 92037
      • Foundation for Cardiovascular Medicine
    • National City, California, United States, 91950
      • Precision Research Institute
    • Torrance, California, United States, 90509
      • Harbor-UCLA Medical Center
    • Torrance, California, United States, 90502
      • Paradigm Clinical Research Institute, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Merritt, Florida, United States, 32952
      • Brevard Cardiovascular Research Associates
    • Miami, Florida, United States, 33144
      • SouthCoast Research Center, Inc
    • Miami, Florida, United States, 33156
      • Molecular Imaging Research and Clinical Trials
    • Miami, Florida, United States, 33165
      • Integrity Clinical Trials
    • Miami Beach, Florida, United States, 33140
      • Newphase Clinical Trials, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Peninsula Research, Inc.
    • Sarasota, Florida, United States, 34239
      • Cardiovascular Center of Sarasota
    • Tampa, Florida, United States, 33617
      • Jedidiah Clinical Research
  • Georgia
    • Athens, Georgia, United States, 30606
      • Athens Heart Center
    • Atlanta, Georgia, United States, 30342
      • Atlanta Clinical Research Center
    • Atlanta, Georgia, United States, 30342
      • Ellipsis Research
  • Kentucky
    • Campbellsville, Kentucky, United States, 42718
      • Central Cardiology
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Alexandria Cardiology Clinic
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Science Center, Tulane University Heart & Vascular Institute
  • New York
    • New York, New York, United States, 10016
      • Manhattan Medical Research Practice
  • Ohio
    • Medina, Ohio, United States, 44256
      • Cleveland Clinic
  • Oregon
    • Hillsboro, Oregon, United States, 97123
      • Hillsboro Cardiology, PC
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Kore CV Research
    • Tullahoma, Tennessee, United States, 37388
      • Tennessee Center for Clinical Trials
  • Texas
    • Houston, Texas, United States, 77070
      • Northwest Houston Cardiology
    • Houston, Texas, United States, 77025
      • AngioCardiac Care of Texas, PA
    • Katy, Texas, United States, 77450
      • Cardiology Center of Houston, PA
    • Tomball, Texas, United States, 77375
      • Northwest Heart Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent.
2. Males and females between the ages of 20 and 80 years.
3. Females of childbearing potential must have a negative pregnancy test, not be breast feeding and established on a method of contraception that in the investigator's opinion is acceptable. Females must agree to remain on their established method of contraception through their participation in the study and for 14 days following the last dose of study drug.
4. Evidence of coronary artery disease that consists of a well-documented medical history (over 3 months prior to the enrolment) of myocardial infarction or significant coronary artery disease with noninvasive or angiographic confirmation.
5. Symptoms that support the diagnosis of chronic angina and/or a history of an abnormal exercise response limited by angina and/or electrocardiograph (ECG) changes.
6. Moderate angina pectoris (Class II or III, Grading of Angina Pectoris by the Canadian Cardiovascular Society Classification System).
7. Patient whose symptom-limited Total Exercise Duration (TED) is between 3 to 7 minutes in Exercise Tolerance Test (ETT) on Standard Bruce Protocol, and symptom-limited TED on two screen examinations (Day -7 and 0) in which the shorter is within 85% of the longer .
8. Patient has been on one beta-blocker or on one calcium-channel blocker for at least 14 days prior to dosing of study medication and can remain on this treatment throughout the study as background anti-anginal treatment. Short-acting nitroglycerin for on-demand use is allowed for all eligible patients.
9. Understand and be willing, able and likely to comply with all study procedures and restrictions and comprehends the verbal rating scales and diary cards.

Exclusion Criteria:

1. With contraindication to, unable to, or with other co-morbidities that may prevent or interfere with the ability to perform treadmill ETT (including, but not limited to: pulmonary hypertension, functionally limiting COPD (chronic obstructive pulmonary disease), history of pulmonary tuberculosis, prior hospitalization for acute exacerbation of chronic lung disease, home oxygen use, chronic oral steroid therapy that can limit exercise capacity, functionally limiting peripheral artery disease, etc.).
2. Presence of electrocardiographic or other abnormalities/factors that could interfere with exercise electrocardiograph interpretation or may lead to a false positive stress test (e.g., pre-exercise horizontal or down-sloping ST segment depression in any standard lead, cardiac glycoside therapy, Lown-Ganong-Levine Syndrome, Wolff-Parkinson-White syndrome (WPW), left bundle branch block, left ventricular hypertrophy with repolarization abnormality, implanted pacemaker, etc.).
3. Clinically significant arrhythmias or atrioventricular conduction block greater than first degree, decompensated heart failure, atrial fibrillation, hypertrophic cardiomyopathy.
4. Acute coronary syndrome (acute myocardial infarction or unstable angina) in the prior 2 months or coronary revascularization within the prior 6 months or planned coronary revascularization during the study period.
5. Congenital cardiac defects, ongoing history of decompensated congestive heart failure, severe valvular disease, severe uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg), severe anemia, suspected or known dissecting aortic aneurysm, acute myocarditis or pericarditis, thrombophlebitis or pulmonary embolism.
6. History of bleeding diathesis, cerebral hemorrhage, or seizure disorders that required anticonvulsant medication.
7. Patients requiring the use of long-acting nitroglycerin, ranolazine, and/or multiple anti-anginal drugs.
8. Aspirin and/or statins started less than 14 days prior to the signing of informed consent.
9. Pregnancy or lactation.
10. Clinical trials/experimental medication 1) Participation in any other clinical trial or receipt of an investigational drug within 30 days prior to the initial visit.

2) Previous participation in the studies of T89. 11. Substance abuse. Patients with a recent history (within the last 2 years) of alcoholism or known drug dependence.

12. Is a family member or relative of the study site staff. 13. Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T89 high dose; T89 225mg bid	Drug: T89 high dose; 225mg bid; Other Names: Dantonic®; Compound Danshen Dripping Pills; Salvtonic®
Experimental: T89 low dose; T89 150mg bid	Drug: T89 Low dose; 150mg bid; Other Names: Dantonic®; Salvtonic®; Compound Danshen Dripping Pill
Experimental: Sanqi+Bingpian; 225mg bid	Drug: Sanqi+Bingpian; 225 mg bid
Placebo Comparator: Placebo; 225mg bid	Drug: Placebo; 225mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of symptom-limited TED from baseline compared to placebo at the end of week 4.	The change of symptom-limited Total Exercise Duration (TED) at trough drug levels at the end of the 4th week of treatment from screen baseline on Standard Bruce Protocol compared with placebo.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks	The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks of treatment from screen baseline on Standard Bruce Protocol compared with placebo;	2nd weeks and 6th weeks
Frequency of weekly angina episodes	Frequency of weekly angina episodes	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to onset of angina during Excise Tolerance Test (ETT);	Time to onset of angina during ETT;	6 weeks

Collaborators and Investigators

• Sponsor: Tasly Pharmaceuticals, Inc.
• Investigators: Study Director: Henry He Sun, PhD, Tasly Group, Co. Ltd.

Publications and helpful links

General Publications

• Shi Y, Liu D, Yuan J, Yan L, Zhan Z, Pan D, Lin L, Mu B. Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice. Evid Based Complement Alternat Med. 2020 Jul 3;2020:5368657. doi: 10.1155/2020/5368657. eCollection 2020.

Helpful Links

• manufacture and sponsor

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: July 19, 2012
• First Submitted That Met QC Criteria: August 5, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Angina Pectoris Treatment Prevention
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: T89-07-CAESA; T89-07-GL (Other Identifier: Tasly Pharmaceuticals INC.)