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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Clinical Study of Effects of Sodium Tanshinone IIA Sulfonate on Pulmonary Hypertension

Conditions
-----------------
Pulmonary Hypertension, Pulmonary Arterial Hypertension, Cardiovascular Diseases, Lung Diseases, 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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet the condition of mean pulmonary arterial pressure (mPAP) ≥25 mmHg at seal level at rest and pulmonary capillary wedge pressure(PCWP)≤15mmHg; 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) ; Male or female between 15 to 70 years old; WHO pulmonary hypertension functional class II or III; The baseline 6-minute walk distance between 150-550 m; 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; Patients receiving sildenafil treatment only previously, or those without target drugs treatment during the past 3 months; Patients or their guardians should agree with this clinical trail and medical informed consent of the trial should be signed. Exclusion Criteria: Unavailable or limited legal capacity; Pregnant or lactational women; Important organs with severe diseases; Mental or physical disability; With suspected or indeed alcohol, drug abuse history; With allergic constitution, with two or more drugs or foods allergy history or those who are allergic to any components of the experimental drugs; 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; Those with systemic blood pressure<90/50 mmHg, or those uncontrolled dangerous hypertension(BP>170/110 mmHg); Patients at active stages of infectious or other diseases such as hepatitis A, hepatitis B, AIDS, tuberculosis, and some connective tissue diseases; Patients with severe infection, especially pulmonary infection; Patients with shock or astable hemodynamics with other causes; Patients with hepatic cirrhosis, and hepatic cirrhosis induced portal hypertension; Patients with severe hemorrhage, and hemorrhagic tendency; Patients who need to take or be taking drugs possible or indeed affecting this trial; Patients cannot accomplish required items (especially 6MWD) because of acute/chronic organic disease (excluding dyspnea) or other illnesses such as lower extremity diseases; Patients with any other conditions considered cannot be recruited.

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 20 mg sildenafil citrate tablets by mouth<br>20 mg sildenafil citrate tablets by mouth three times a day for 8 weeks | Drug: 20 mg sildenafil citrate by mouth<br>* 20 mg sildenafil citrate tablets by mouth three times a day for 8 weeks<br>* Other names: Viagra;|
| Experimental: sodium tanshinone IIA sulfonate, sildenafil citrate tablets<br>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<br>* 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<br>* Other names: Viagra;|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sodium tanshinone IIA sulfonate, pulmonary hypertension