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

Cardiovascular Diseases Clinical Trial

— STS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01637675
• Other study ID #: STS-PH01
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: July 1, 2012
• Last updated: March 28, 2014
• Start date: May 2013
• Est. completion date: December 2014

Study information

• Verified date: March 2014
• Source: The First Affiliated Hospital of Guangzhou Medical University
• Contact: Jian Wang, MD
• Phone: +8615013388183
• Email: jwang31[@]jhmi.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Hypertension
• Hypertension, Pulmonary
• Lung Diseases
• Pulmonary Arterial Hypertension
• Pulmonary Hypertension
• Tanshinone IIA Sulfonate

Intervention

Drug:
• 20 mg sildenafil citrate by mouth
20 mg sildenafil citrate tablets by mouth three times a day for 8 weeks
• 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

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (11)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	Yes
Other	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	No
Primary	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	No
Secondary	WHO functional class of pulmonary hypertension(PH)		At the end of 0-,2-, 4-,6- and 8-week of trial	No
Secondary	Borg dyspnea score		At the end of 0-, 2-,4-,6- and 8-week trial	No
Secondary	Minnesota living with heart failure questionnaire		At the end of 0-,2-, 4-,6- and 8-week trial	No
Secondary	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	No
Secondary	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	No