Efficacy and Safety Study of Sodium Tanshinone IIA Sulfonate on Pulmonary Hypertension (STS)

Clinical Study of Effects of Sodium Tanshinone IIA Sulfonate on Pulmonary Hypertension

Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the main pharmacologically active natural compound from a traditional Chinese herbal medicine,the dried root of Salvia miltiorrhiza Bunge known as Danshen. Danshen has been known for the function of improving body functions such as activating blood circulation and removing blood stasis according to the theory of traditional Chinese medicine. Danshen and its various formula products including STS have been long-time widely used in oriental countries, especially China to treat various inflammatory and cardiovascular diseases for its pharmacological actions, including vasodilatation, anticoagulation, anti-inflammation, and free radical scavenging,with negligible adverse effects observed.

The investigator's objective is to evaluate whether STS exhibits beneficial effects on pulmonary hypertension. This is a randomized, controlled, multicentre clinical trial study. 90 patients with pulmonary hypertension will be enrolled in this study.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Pulmonary Hypertension; Tanshinone IIA Sulfonate
• Intervention / Treatment: Drug: 20 mg sildenafil citrate by mouth; Drug: sodium tanshinone IIA sulfonate diluted with 5% glucose solution,20mg sildenafil citrate by mouth

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jian Wang, MD; Phone Number: +8615013388183; Email: jwang31@jhmi.edu

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Jian Wang, MD; Phone Number: +8615013388183; Email: jwang31@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Meet the condition of mean pulmonary arterial pressure (mPAP) ≥25 mmHg at seal level at rest and pulmonary capillary wedge pressure(PCWP)≤15mmHg;
2. Category 1 or 4 of PH in stable stage according to 2008 Dana Point Conference,including the idiopathic, hereditary, drugs and toxins induced, associated with connective tissue disease or congenital heart disease, and chronic thromboembolic pulmonary arterial hypertension(PAH) ;
3. Male or female between 15 to 70 years old;
4. WHO pulmonary hypertension functional class II or III;
5. The baseline 6-minute walk distance between 150-550 m;
6. Patients' condition should be stable for more than one month after basic treatment; For those patients with congenital heart disease, surgery should have been performed six months or more before they are enrolled in the study;
7. Patients receiving sildenafil treatment only previously, or those without target drugs treatment during the past 3 months;
8. Patients or their guardians should agree with this clinical trail and medical informed consent of the trial should be signed.

Exclusion Criteria:

1. Unavailable or limited legal capacity;
2. Pregnant or lactational women;
3. Important organs with severe diseases;
4. Mental or physical disability;
5. With suspected or indeed alcohol, drug abuse history;
6. With allergic constitution, with two or more drugs or foods allergy history or those who are allergic to any components of the experimental drugs;
7. With both aspartate aminotransferase (AST) and glutamic-pyruvic transaminase (ALT) more than three times of the upper limit of normal in liver function test and Ccr≤50ml/min in kidney function test;
8. Those with systemic blood pressure<90/50 mmHg, or those uncontrolled dangerous hypertension(BP>170/110 mmHg);
9. Patients at active stages of infectious or other diseases such as hepatitis A, hepatitis B, AIDS, tuberculosis, and some connective tissue diseases;
10. Patients with severe infection, especially pulmonary infection;
11. Patients with shock or astable hemodynamics with other causes;
12. Patients with hepatic cirrhosis, and hepatic cirrhosis induced portal hypertension;
13. Patients with severe hemorrhage, and hemorrhagic tendency;
14. Patients who need to take or be taking drugs possible or indeed affecting this trial;
15. Patients cannot accomplish required items (especially 6MWD) because of acute/chronic organic disease (excluding dyspnea) or other illnesses such as lower extremity diseases;
16. Patients with any other conditions considered cannot be recruited.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 20 mg sildenafil citrate tablets by mouth; 20 mg sildenafil citrate tablets by mouth three times a day for 8 weeks	Drug: 20 mg sildenafil citrate by mouth; 20 mg sildenafil citrate tablets by mouth three times a day for 8 weeks; Other Names: Viagra
EXPERIMENTAL: sodium tanshinone IIA sulfonate, sildenafil citrate tablets; sodium Tanshinone IIA sulfonate injection 80 mg diluted with 5% glucose solution(0.9% sodium chloride injection also permitted if necessary) 250ml ivdrip once a day for 8 weeks,20mg sildenafil citrate tablets by mouth three times a day for the same duration	Drug: sodium tanshinone IIA sulfonate diluted with 5% glucose solution,20mg sildenafil citrate by mouth; sodium Tanshinone IIA sulfonate injection 80 mg diluted with 5% glucose solution(0.9% sodium chloride injection will also be permitted if necessary) 250ml iv drip once a day for 8 weeks,as well as 20mg sildenafil citrate tablets by mouth three times a day for the same duration of treatment; Other Names: Viagra; Sodium tanshinone IIA sulfonate injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mPAP by right heart catheterization	To assess if sodium Tanshinone IIA sulfonate decreases mean pulmonary arterial pressure.	At the end of 0- and 8-week trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WHO functional class of pulmonary hypertension(PH)		At the end of 0-,2-, 4-,6- and 8-week of trial
Borg dyspnea score		At the end of 0-, 2-,4-,6- and 8-week trial
Minnesota living with heart failure questionnaire		At the end of 0-,2-, 4-,6- and 8-week trial
6-minute walk distance (6MWD)	To assess if sodium Tanshinone IIA sulfonate improves the exercise capacity of patients with pulmonary hypertension.	At the end of 0-, 2-, 4-, 6- and 8-week trial
Pulmonary vascular resistance(PVR) measured by right heart catheterization	PVR is used to evaluate whether STS decreases mPAP or increases pulmonary circulatory blood flow.	At the end of 0- and 8-week trial

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The level of N terminal-proBNP(NT-proBNP),cardiac troponin I(cTnI) and uric acid(UA) in serum	The three indicators are used to evaluate whether STS alleviates right heart failure.	At the end of 0-,4- and 8-week trial
Indicators monitoring STS safety	The blood routine test,urine routine test,liver and kidney function and blood clotting function will be examined and some worsening events,such as death,PH aggravation,need to add other unscheduled target drugs,need to be hospitalized or prolonged hospitalization,lung and/or heart transplantation and/or any other severe adverse events surely or very likely due to STS,will be closely observed as the safety indications of STS.	At the end of 0-,4- and 8-week trial
Other hemodynamic parameters measured by right heart catheterization	To evaluate whether STS has beneficial effects on hemodynamic parameters.	At the end of 0- and 8-week trial

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangzhou Medical University
• Collaborators: The Affiliated Hospital of Qingdao University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Beijing Chao Yang Hospital; The First Affiliated Hospital of Zhengzhou University; Guangdong Provincial People's Hospital; Beijing Anzhen Hospital; Second Affiliated Hospital of Xi'an Jiaotong University; Sir Run Run Shaw Hospital; Dongguan People's Hospital; Jiangsu Carefree Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ANTICIPATED): December 1, 2014
• Study Completion (ANTICIPATED): December 1, 2014

Study Registration Dates

• First Submitted: July 1, 2012
• First Submitted That Met QC Criteria: July 7, 2012
• First Posted (ESTIMATE): July 11, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 31, 2014
• Last Update Submitted That Met QC Criteria: March 28, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: pulmonary hypertension; sodium tanshinone IIA sulfonate
• Additional Relevant MeSH Terms: Vascular Diseases; Respiratory Tract Diseases; Hypertension; Cardiovascular Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Anti-Infective Agents; Peripheral Nervous System Agents; Urological Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Anticoagulants; Phosphodiesterase Inhibitors; Chelating Agents; Sequestering Agents; Phosphodiesterase 5 Inhibitors; Calcium Chelating Agents; Sildenafil Citrate; Citric Acid; Sodium Citrate; Tanshinone
• Other Study ID Numbers: STS-PH01