SepsisHH-SACNCT07897006
Safflower (Carthamus Tinctorius L.) Granules for Sepsis-associated Coagulopathy
A study testing High-dose safflower granules and Medium-dose safflower granules in people with Sepsis and Disseminated Intravascular Coagulation (DIC), run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
Sepsis is a life-threatening condition in which infection triggers widespread inflammation and blood clotting abnormalities. Many patients with sepsis develop coagulopathy (impaired blood clotting), which contributes to organ damage and death. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sepsis, Disseminated Intravascular Coagulation (DIC)
- What is being tested?
- High-dose safflower granules and Medium-dose safflower granules
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 210 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2026to 31 Aug 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 and <= 80 years at admission
- Meeting the Sepsis 3.0 diagnostic criteria, defined as infection-induced organ dysfunction with an increase in the Sequential Organ Failure Assessment (SOFA) score of >= 2 points from baseline
- Coagulopathy at admission, defined as fibrin degradation products (FDP) > 9.9 mg/L AND D-dimer > 3.3 mg/L
- Written informed consent obtained from the patient or legal representative
Who cannot join
- Pregnant or lactating women
- Known allergy or hypersensitivity to Carthamus tinctorius L. (safflower)
- Hematological disorders, autoimmune diseases, or advanced malignancy
- Current treatment with anticoagulant or antiplatelet agents for underlying conditions before admission
- Confirmed venous thromboembolism
- Conditions with potential bleeding risk, including severe traumatic brain injury, cerebral aneurysm, arteriovenous malformation, bronchiectasis, or gastrointestinal ulcer; or within 24 hours of severe trauma or major surgery
Show all 10Show fewer
- Pre-existing chronic organ failure: cardiac failure (long-term left ventricular assist device or inotropic agents); hepatic failure (Child-Pugh class C); chronic respiratory failure (long-term home oxygen or non-invasive ventilation); chronic renal failure (glomerular filtration rate < 30 mL/min/1.73m2, or regular hemodialysis)
- Requirement for any form of blood purification therapy or extracorporeal membrane oxygenation (due to mandatory anticoagulation)
- Life expectancy < 48 hours
- Participation in other interventional clinical trials within the study period
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Emergency Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality
Li Ma, MD, PhD, +86-15921615410, Malipostgraduate2@163.com
About this study
Official title: Efficacy of Safflower (Carthamus Tinctorius L.) Granules in Patients With Sepsis-associated Coagulopathy: a Randomized, Double-blind, Controlled, Three-arm Trial
Sepsis is a life-threatening condition in which infection triggers widespread inflammation and blood clotting abnormalities. Many patients with sepsis develop coagulopathy (impaired blood clotting), which contributes to organ damage and death. Safflower (Carthamus tinctorius L.) is a traditional Chinese medicine herb with documented anticoagulant, anti-platelet, and blood vessel-protective properties. This randomized, double-blind, placebo-controlled trial will enroll 210 adult patients with sepsis-associated coagulopathy at Ruijin Hospital. Participants will be randomly assigned to one of three groups: high-dose safflower granules (equivalent to 9 g of raw herb daily), medium-dose safflower granules (equivalent to 6 g of raw herb daily), matching placebo (equivalent to 0.6 g of raw herb daily for blinding). The granules are dissolved in 50 mL of warm water and given through a nasogastric tube once daily for 7 days, in addition to standard sepsis treatment. The primary outcome is the improvement in the SOFA score (a measure of organ function) at 14 days. Secondary outcomes include DIC scores, coagulation tests, endothelial injury and platelet markers, inflammatory markers, 28-day mortality, length of ICU and hospital stay, and adverse events. The study is funded by Ruijin Hospital as an investigator-initiated trial.
Read the detailed description
Background: Sepsis remains a leading cause of mortality in intensive care units. Disseminated intravascular microthrombosis secondary to vascular endothelial injury plays a pivotal role in the progression to multiple organ dysfunction syndrome. Safflower (Carthamus tinctorius L.), a traditional Chinese medicine, exhibits anticoagulant, anti-platelet, endothelium-protective, and anti-inflammatory pharmacological activities, largely attributed to its principal active constituent hydroxysafflor yellow A (HSYA).
Design: This is a single-center, prospective, randomized, double-blind, three-arm trial. The comparator is a one-tenth-dose safflower preparation serving blinding only. Adults (18-80 years) meeting Sepsis 3.0 criteria with coagulopathy at admission (FDP > 9.9 mg/L and D-dimer > 3.3 mg/L) will be enrolled after written informed consent.
Interventions: Participants are randomized 1:1:1 by block randomization (generated with the sample function in R by an independent statistician) to: (1) high-dose group: safflower granules equivalent to 9 g of raw herb once daily; (2) medium-dose group: safflower granules equivalent to 6 g of raw herb once daily; (3) control group: matching placebo granules containing one-tenth of the safflower dose (equivalent to 0.6 g of raw herb), prepared solely for blinding and not intended as a therapeutic dose. All study medications are provided in sealed, coded envelopes to preserve blinding; before administration, granules are dissolved in 50 mL of warm water and instilled via nasogastric tube for 7 consecutive days or until clinical stabilization. Allocation concealment is maintained by sequentially numbered opaque envelopes opened only by an unblinded drug administrator. All groups receive guideline-directed standard sepsis care (Surviving Sepsis Campaign). Treatment assignment is unblinded only for serious adverse events requiring knowledge of treatment, with ethics committee approval.
Outcomes: The primary outcome is the change in SOFA score from baseline to Day 14. Secondary outcomes include ISTH-DIC scores, coagulation parameters, endothelial injury markers, platelet function markers, and inflammatory markers (Days 1, 2, 3, 5, 7, 14), 28-day all-cause mortality, duration of organ support, ICU and hospital length of stay, and adverse events through Day 28.
Sample size: A feasibility-based sample size of 70 patients per group (210 total) was calculated assuming a 10% reduction in 7-day SOFA score (SD 1.5, alpha 0.05, power 80%), allowing for 10% dropout.
Analysis: The intention-to-treat population will be analyzed. The primary outcome will be compared among the three groups using ANOVA or the Kruskal-Wallis test with post-hoc pairwise comparisons and multiplicity adjustment. Kaplan-Meier curves with the log-rank test will be used for survival outcomes.
- Being tested
- High-dose safflower granules, Medium-dose safflower granules, Placebo granules (one-tenth of medium-dose safflower)
- Keywords
- Carthamus tinctorius, Safflower, Chinese herbal medicine, Disseminated intravascular coagulation, SOFA score, Traditional Chinese Medicine, Sepsis-Associated Coagulopathy
- Medical subject headings
- Sepsis, Disseminated Intravascular Coagulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose safflower granulesOther
Also called Carthamus tinctorius L. granules
Safflower (Carthamus tinctorius L.) granules equivalent to 9 g of raw herb, prepared as a blinded study medication in a sealed coded envelope. Immediately before administration the granules are dissolved in 50 mL of warm water and instilled via nasogastric tube once daily for 7 consecutive days or until clinical stabilization. All participants in this arm also receive standard-of-care sepsis treatment per the Surviving Sepsis Campaign guidelines, including early antimicrobial therapy, goal-directed fluid resuscitation, and organ support as needed.
Medium-dose safflower granulesOther
Also called Carthamus tinctorius L. granules
Safflower (Carthamus tinctorius L.) granules equivalent to 6 g of raw herb, prepared as a blinded study medication in a sealed coded envelope. Immediately before administration the granules are dissolved in 50 mL of warm water and instilled via nasogastric tube once daily for 7 consecutive days or until clinical stabilization. All participants in this arm also receive standard-of-care sepsis treatment per the Surviving Sepsis Campaign guidelines, including early antimicrobial therapy, goal-directed fluid resuscitation, and organ support as needed.
Placebo granules (one-tenth of medium-dose safflower)Other
Safflower granules at one-tenth of the medium dose (equivalent to 0.6 g of raw herb), prepared to match the study granules in appearance and odor for blinding, in a sealed coded envelope. Immediately before administration the granules are dissolved in 50 mL of warm water and instilled via nasogastric tube once daily, for the same duration as the safflower arms, plus standard-of-care sepsis treatment per the Surviving Sepsis Campaign guidelines.
| Study group | Role | What they receive |
|---|---|---|
| High-Dose Safflower | Experimental | Safflower (Carthamus tinctorius L.) granules equivalent to 9 g of raw herb, dissolved in 50 mL of warm water and given via nasogastric tube once daily for 7 consecutive days or until clinical stabilization, plus standard-of-care sepsis treatment. Receives: Other: High-dose safflower granules |
| Medium-Dose Safflower | Experimental | Safflower (Carthamus tinctorius L.) granules equivalent to 6 g of raw herb, dissolved in 50 mL of warm water and given via nasogastric tube once daily for 7 consecutive days or until clinical stabilization, plus standard-of-care sepsis treatment. Receives: Other: Medium-dose safflower granules |
| Placebo granules (one-tenth of medium-dose safflower) | Placebo comparator | Safflower (Carthamus tinctorius L.) granules at one-tenth of the medium dose (equivalent to 0.6 g of raw herb), dissolved in 50 mL of warm water and given via nasogastric tube once daily, same duration as the safflower groups, plus standard-of-care sepsis treatment. The one-tenth dose serves blinding by matching the appearance and odor of the study granules. Receives: Other: Placebo granules (one-tenth of medium-dose safflower) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in SOFA score from baseline to Day 14
The Sequential Organ Failure Assessment (SOFA) score is a measure of organ dysfunction (range 0-24, higher scores indicate more severe dysfunction). The primary endpoint is the improvement value defined as the baseline SOFA score minus the Day 14 SOFA score, compared among the three groups. SOFA scores are assessed at baseline (before the first dose) and on Day 14. Component-level scores are reported separately as a pre-specified supportive outcome.
Measured: From baseline (before the first dose) through Day 14
Secondary outcomes (31)
Change in ISTH-DIC score from baseline to Day 14
The International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation score, calculated at each assessment time point from platelet count, prothrombin time, fibrinogen, and D-dimer (or fibrin degradation products); a total score of 5 or more indicates overt DIC. Analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
All-cause mortality at 28 days
All-cause mortality is defined as death from any cause within 28 days after randomization, counted for all randomized participants regardless of causality assessment. Vital status at Day 28 is collected for all participants.
Measured: 28 days after randomization
ICU length of stay and total hospital length of stay
Duration of intensive care unit stay and total hospital stay, measured in days from randomization to ICU discharge and to hospital discharge or death, respectively, for all randomized participants.
Measured: From randomization to hospital discharge or through study completion, an average of approximately 22 days
Change in SOFA Component Scores for Hepatic, Renal, Respiratory, and Cardiovascular Function from Baseline to Day 14
The total SOFA score (0-24) is the primary endpoint of this study; this outcome reports the pre-specified component-level analysis supporting it. The SOFA score grades six organ systems, each 0-4 points. This outcome reports the hepatic (serum total bilirubin), renal (serum creatinine or receipt of renal replacement therapy), respiratory (PaO2/FiO2 ratio), and cardiovascular (mean arterial pressure and vasopressor use) components, each scored 0-4 per the SOFA definitions in the Sepsis-3 criteria. Change is calculated as baseline minus the Day N score, consistent with the primary endpoint direction, so positive values indicate improvement; components are reported individually in points.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) from Baseline to Day 14
Prothrombin time (PT, seconds) and activated partial thromboplastin time (APTT, seconds) measured from venous blood samples collected at each protocol-specified time point.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in International Normalized Ratio (INR) from Baseline to Day 14
The international normalized ratio (INR), calculated from the prothrombin time and the international sensitivity index (ISI) of the thromboplastin reagent used, reported as a dimensionless ratio; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Fibrinogen (FG) from Baseline to Day 14
Plasma fibrinogen concentration measured in venous blood samples collected at each protocol-specified time point, reported in g/L; analyzed as change from baseline. Fibrinogen is both an acute-phase reactant and the substrate of fibrin formation.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in D-dimer from Baseline to Day 14
Plasma D-dimer, a marker of endogenous fibrin formation and degradation, measured in venous blood samples collected at each protocol-specified time point, reported in mg/L; analyzed as change from baseline. Elevated D-dimer at screening is an eligibility criterion of this study.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Platelet Count from Baseline to Day 14
Platelet count measured in venous blood samples collected at each protocol-specified time point, reported as 10^9/L; analyzed as change from baseline. Platelet count is also a component of the ISTH-DIC score.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Antithrombin III (AT III), Protein C Activity, and Coagulation Factor Activities (FV, FVII, FVIII) from Baseline to Day 14
Antithrombin III activity, protein C activity, and coagulation factor V, VII, and VIII activities measured in citrated plasma at each protocol-specified time point, all reported as percent activity; each analyte analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in PAI-1, T-PAIC, and t-PA from Baseline to Day 14
Plasma plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator-inhibitor complex (T-PAIC), and tissue-type plasminogen activator (t-PA) measured in venous blood samples at baseline and on Day 14, all reported in ng/mL; each analyte analyzed as change from baseline. Together these characterize fibrinolytic activity and its inhibition.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Plasmin-alpha2 Plasmin Inhibitor Complex (PIC) from Baseline to Day 14
Plasma plasmin-alpha2 plasmin inhibitor complex (PIC), a marker of endogenous fibrinolysis, measured in venous blood samples at baseline and on Day 14, reported in ug/L; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Thromboelastography (TEG) Reaction Time (R) and Kinetics Time (K) from Baseline to Day 14
Thromboelastography (TEG) R time, reflecting the rate of initial fibrin formation, and K time, reflecting the kinetics of clot strengthening, performed on citrated whole blood at baseline and on Day 14, both reported in minutes; each parameter analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Thromboelastography (TEG) Alpha Angle from Baseline to Day 14
Thromboelastography (TEG) alpha angle, reflecting the speed of fibrin build-up and thrombin activity, performed on citrated whole blood at baseline and on Day 14, reported in degrees; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Thromboelastography (TEG) Maximum Amplitude (MA) from Baseline to Day 14
Thromboelastography (TEG) maximum amplitude (MA), reflecting the strength of the platelet-fibrin clot and overall platelet function, performed on citrated whole blood at baseline and on Day 14, reported in millimeters; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Thrombomodulin (TM), Thrombin-Antithrombin Complex (TAT), and ICAM-1 from Baseline to Day 14
Plasma thrombomodulin (TM), thrombin-antithrombin complex (TAT), and intercellular adhesion molecule-1 (ICAM-1) measured in venous blood samples at baseline and on Day 14, all reported in ng/mL; each analyte analyzed as change from baseline. TAT reflects in vivo thrombin generation, while TM and ICAM-1 reflect endothelial injury and activation.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in von Willebrand Factor (VWF) from Baseline to Day 14
Plasma von Willebrand factor (VWF), an established marker of endothelial activation that mediates platelet adhesion, measured in venous blood samples at baseline and on Day 14, reported in IU/dL; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Endothelin-1 (ET-1) and Angiopoietin-2 (ANG-2) from Baseline to Day 14
Plasma endothelin-1 (ET-1) and angiopoietin-2 (ANG-2) measured in venous blood samples at baseline and on Day 14, both reported in pg/mL; each analyte analyzed as change from baseline. Both markers reflect endothelial dysfunction and vascular permeability.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Aggregation Rate and Platelet Adhesion Rate from Baseline to Day 14
ADP-induced and collagen-induced platelet aggregation rates and the platelet adhesion rate, measured in blood samples at baseline and on Day 14, all reported as percentages; each measure analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Surface P-selectin (CD62P) from Baseline to Day 14
Platelet surface P-selectin (CD62P) expression, reported as percent mean fluorescence intensity (MFI) by flow cytometry, measured at baseline and on Day 14; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Factor 4 (PF4) from Baseline to Day 14
Plasma platelet factor 4 (PF4), a marker of platelet activation, measured in venous blood samples at baseline and on Day 14, reported in ng/mL; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in GP IIb/IIIa Receptor Activity, GP Ib Receptor Expression, and VWF-Platelet Binding Capacity from Baseline to Day 14
Glycoprotein IIb/IIIa receptor activity, glycoprotein Ib receptor expression, and the VWF-platelet binding capacity (binding index), measured in blood samples at baseline and on Day 14, all reported as percentages; each measure analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Mean Platelet Volume (MPV) from Baseline to Day 14
Mean platelet volume (MPV), a marker of platelet activation and thrombopoiesis, measured in venous blood samples at baseline and on Day 14, reported in fL; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Distribution Width (PDW) and Immature Platelet Fraction (IPF) from Baseline to Day 14
Platelet distribution width (PDW) and immature platelet fraction (IPF), measured in venous blood samples at baseline and on Day 14, both reported as percentages; each analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in White Blood Cell Count (WBC) from Baseline to Day 14
White blood cell count measured in venous blood samples collected at each protocol-specified time point, reported as 10^9/L; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in C-reactive Protein (CRP) from Baseline to Day 14
Serum C-reactive protein (CRP), a sensitive systemic inflammation marker in sepsis, measured at each protocol-specified time point, reported in mg/L; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Procalcitonin (PCT) from Baseline to Day 14
Serum procalcitonin (PCT), used to gauge bacterial infection burden and sepsis severity, measured at each protocol-specified time point, reported in ng/mL; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Cytokines IL-2 Receptor, IL-1β, IL-8, and IL-10 from Baseline to Day 14
Plasma interleukin-2 receptor, interleukin-1 beta (IL-1β), interleukin-8 (IL-8), and interleukin-10 (IL-10) measured in venous blood samples at baseline and on Day 14, reported in ug/L; each cytokine analyzed as change from baseline. These represent the pro-inflammatory and anti-inflammatory arms of the cytokine response.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Interleukin-6 (IL-6) from Baseline to Day 14
Plasma interleukin-6 (IL-6), a central pro-inflammatory cytokine linking inflammation and coagulation activation, measured in venous blood samples at baseline and on Day 14, reported in ng/L; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Change in Tumor Necrosis Factor-alpha (TNF-α) from Baseline to Day 14
Plasma tumor necrosis factor-alpha (TNF-α) measured in venous blood samples at baseline and on Day 14, reported in pg/mL; analyzed as change from baseline.
Measured: From baseline through Day 14, assessed on Days 0 and 14
Number of days of organ function support (vasopressors, mechanical ventilation, or renal replacement therapy)
Number of days receiving organ function support, including vasopressors, mechanical ventilation, and renal replacement therapy, counted for all randomized participants from randomization; each support type analyzed separately.
Measured: From randomization to hospital discharge or through study completion, an average of approximately 22 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Three-arm parallel randomized trial (high-dose safflower, medium-dose safflower, placebo), 1:1:1 allocation.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li Ma, Ruijin Hospital
- Investigators
- Li Ma, MD, PhD, Study director, Emergency Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07897006
- Sponsor's protocol ID
- MR-31-26-022057
- Other IDs
- 2026-112
- Acronym
- HH-SAC
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Safflower (Carthamus Tinctorius L.) Granules in Patients With Sepsis-associated Coagulopathy: a Randomized, Double-blind, Controlled, Three-arm Trial
- ClinicalTrials.gov ID
- NCT07897006
- Acronym / sponsor ID
- HH-SAC / MR-31-26-022057
- Keywords
- Carthamus tinctorius, Safflower, Chinese herbal medicine, Disseminated intravascular coagulation, SOFA score, Traditional Chinese Medicine, Sepsis-Associated Coagulopathy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 27 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sepsis is a life-threatening condition in which infection triggers widespread inflammation and blood clotting abnormalities. Many patients with sepsis develop coagulopathy (impaired blood clotting), which contributes to organ damage and death. Safflower (Carthamus tinctorius L.) is a traditional Chinese medicine herb with documented anticoagulant, anti-platelet, and blood vessel-protective properties. This randomized, double-blind, placebo-controlled trial will enroll 210 adult patients with sepsis-associated coagulopathy at Ruijin Hospital. Participants will be randomly assigned to one of three groups: high-dose safflower granules (equivalent to 9 g of raw herb daily), medium-dose safflower granules (equivalent to 6 g of raw herb daily), matching placebo (equivalent to 0.6 g of raw herb daily for blinding). The granules are dissolved in 50 mL of warm water and given through a nasogastric tube once daily for 7 days, in addition to standard sepsis treatment. The primary outcome is the improvement in the SOFA score (a measure of organ function) at 14 days. Secondary outcomes include DIC scores, coagulation tests, endothelial injury and platelet markers, inflammatory markers, 28-day mortality, length of ICU and hospital stay, and adverse events. The study is funded by Ruijin Hospital as an investigator-initiated trial.
Detailed description
Background: Sepsis remains a leading cause of mortality in intensive care units. Disseminated intravascular microthrombosis secondary to vascular endothelial injury plays a pivotal role in the progression to multiple organ dysfunction syndrome. Safflower (Carthamus tinctorius L.), a traditional Chinese medicine, exhibits anticoagulant, anti-platelet, endothelium-protective, and anti-inflammatory pharmacological activities, largely attributed to its principal active constituent hydroxysafflor yellow A (HSYA).
Design: This is a single-center, prospective, randomized, double-blind, three-arm trial. The comparator is a one-tenth-dose safflower preparation serving blinding only. Adults (18-80 years) meeting Sepsis 3.0 criteria with coagulopathy at admission (FDP > 9.9 mg/L and D-dimer > 3.3 mg/L) will be enrolled after written informed consent.
Interventions: Participants are randomized 1:1:1 by block randomization (generated with the sample function in R by an independent statistician) to: (1) high-dose group: safflower granules equivalent to 9 g of raw herb once daily; (2) medium-dose group: safflower granules equivalent to 6 g of raw herb once daily; (3) control group: matching placebo granules containing one-tenth of the safflower dose (equivalent to 0.6 g of raw herb), prepared solely for blinding and not intended as a therapeutic dose. All study medications are provided in sealed, coded envelopes to preserve blinding; before administration, granules are dissolved in 50 mL of warm water and instilled via nasogastric tube for 7 consecutive days or until clinical stabilization. Allocation concealment is maintained by sequentially numbered opaque envelopes opened only by an unblinded drug administrator. All groups receive guideline-directed standard sepsis care (Surviving Sepsis Campaign). Treatment assignment is unblinded only for serious adverse events requiring knowledge of treatment, with ethics committee approval.
Outcomes: The primary outcome is the change in SOFA score from baseline to Day 14. Secondary outcomes include ISTH-DIC scores, coagulation parameters, endothelial injury markers, platelet function markers, and inflammatory markers (Days 1, 2, 3, 5, 7, 14), 28-day all-cause mortality, duration of organ support, ICU and hospital length of stay, and adverse events through Day 28.
Sample size: A feasibility-based sample size of 70 patients per group (210 total) was calculated assuming a 10% reduction in 7-day SOFA score (SD 1.5, alpha 0.05, power 80%), allowing for 10% dropout.
Analysis: The intention-to-treat population will be analyzed. The primary outcome will be compared among the three groups using ANOVA or the Kruskal-Wallis test with post-hoc pairwise comparisons and multiplicity adjustment. Kaplan-Meier curves with the log-rank test will be used for survival outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Three-arm parallel randomized trial (high-dose safflower, medium-dose safflower, placebo), 1:1:1 allocation.
| Arm | Type | Receives |
|---|---|---|
| High-Dose Safflower | Experimental | Other: High-dose safflower granulesSafflower (Carthamus tinctorius L.) granules equivalent to 9 g of raw herb, dissolved in 50 mL of warm water and given via nasogastric tube once daily for 7 consecutive days or until clinical stabilization, plus standard-of-care sepsis treatment. |
| Medium-Dose Safflower | Experimental | Other: Medium-dose safflower granulesSafflower (Carthamus tinctorius L.) granules equivalent to 6 g of raw herb, dissolved in 50 mL of warm water and given via nasogastric tube once daily for 7 consecutive days or until clinical stabilization, plus standard-of-care sepsis treatment. |
| Placebo granules (one-tenth of medium-dose safflower) | Placebo comparator | Other: Placebo granules (one-tenth of medium-dose safflower)Safflower (Carthamus tinctorius L.) granules at one-tenth of the medium dose (equivalent to 0.6 g of raw herb), dissolved in 50 mL of warm water and given via nasogastric tube once daily, same duration as the safflower groups, plus standard-of-care sepsis treatment. The one-tenth dose serves blinding by matching the appearance and odor of the study granules. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age >= 18 and <= 80 years at admission
- Meeting the Sepsis 3.0 diagnostic criteria, defined as infection-induced organ dysfunction with an increase in the Sequential Organ Failure Assessment (SOFA) score of >= 2 points from baseline
- Coagulopathy at admission, defined as fibrin degradation products (FDP) > 9.9 mg/L AND D-dimer > 3.3 mg/L
- Written informed consent obtained from the patient or legal representative
Key exclusion criteria (10 listed)
- Pregnant or lactating women
- Known allergy or hypersensitivity to Carthamus tinctorius L. (safflower)
- Hematological disorders, autoimmune diseases, or advanced malignancy
- Current treatment with anticoagulant or antiplatelet agents for underlying conditions before admission
- Confirmed venous thromboembolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-dose safflower granulesAlso: Carthamus tinctorius L. granulesSafflower (Carthamus tinctorius L.) granules equivalent to 9 g of raw herb, prepared as a blinded study medication in a sealed coded envelope. Immediately before administration the granules are dissolved in 50 mL of warm water and instilled via nasogastric tube once daily for 7 consecutive days or until clinical stabilization. All participants in this arm also receive standard-of-care sepsis treatment per the Surviving Sepsis Campaign guidelines, including early antimicrobial therapy, goal-directed fluid resuscitation, and organ support as needed. | Other | High-Dose Safflower |
| Medium-dose safflower granulesAlso: Carthamus tinctorius L. granulesSafflower (Carthamus tinctorius L.) granules equivalent to 6 g of raw herb, prepared as a blinded study medication in a sealed coded envelope. Immediately before administration the granules are dissolved in 50 mL of warm water and instilled via nasogastric tube once daily for 7 consecutive days or until clinical stabilization. All participants in this arm also receive standard-of-care sepsis treatment per the Surviving Sepsis Campaign guidelines, including early antimicrobial therapy, goal-directed fluid resuscitation, and organ support as needed. | Other | Medium-Dose Safflower |
| Placebo granules (one-tenth of medium-dose safflower)Safflower granules at one-tenth of the medium dose (equivalent to 0.6 g of raw herb), prepared to match the study granules in appearance and odor for blinding, in a sealed coded envelope. Immediately before administration the granules are dissolved in 50 mL of warm water and instilled via nasogastric tube once daily, for the same duration as the safflower arms, plus standard-of-care sepsis treatment per the Surviving Sepsis Campaign guidelines. | Other | Placebo granules (one-tenth of medium-dose safflower) |
Primary outcome
Change in SOFA score from baseline to Day 14
Time frame: From baseline (before the first dose) through Day 14
The Sequential Organ Failure Assessment (SOFA) score is a measure of organ dysfunction (range 0-24, higher scores indicate more severe dysfunction). The primary endpoint is the improvement value defined as the baseline SOFA score minus the Day 14 SOFA score, compared among the three groups. SOFA scores are assessed at baseline (before the first dose) and on Day 14. Component-level scores are reported separately as a pre-specified supportive outcome.
31 secondary outcomes
Change in ISTH-DIC score from baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
All-cause mortality at 28 days
Time frame: 28 days after randomization
ICU length of stay and total hospital length of stay
Time frame: From randomization to hospital discharge or through study completion, an average of approximately 22 days
Change in SOFA Component Scores for Hepatic, Renal, Respiratory, and Cardiovascular Function from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in International Normalized Ratio (INR) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Fibrinogen (FG) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in D-dimer from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Platelet Count from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Antithrombin III (AT III), Protein C Activity, and Coagulation Factor Activities (FV, FVII, FVIII) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in PAI-1, T-PAIC, and t-PA from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Plasmin-alpha2 Plasmin Inhibitor Complex (PIC) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Thromboelastography (TEG) Reaction Time (R) and Kinetics Time (K) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Thromboelastography (TEG) Alpha Angle from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Thromboelastography (TEG) Maximum Amplitude (MA) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Thrombomodulin (TM), Thrombin-Antithrombin Complex (TAT), and ICAM-1 from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in von Willebrand Factor (VWF) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Endothelin-1 (ET-1) and Angiopoietin-2 (ANG-2) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Aggregation Rate and Platelet Adhesion Rate from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Surface P-selectin (CD62P) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Factor 4 (PF4) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in GP IIb/IIIa Receptor Activity, GP Ib Receptor Expression, and VWF-Platelet Binding Capacity from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Mean Platelet Volume (MPV) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Platelet Distribution Width (PDW) and Immature Platelet Fraction (IPF) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in White Blood Cell Count (WBC) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in C-reactive Protein (CRP) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Procalcitonin (PCT) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0, 1, 2, 3, 5, 7, and 14
Change in Cytokines IL-2 Receptor, IL-1β, IL-8, and IL-10 from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Interleukin-6 (IL-6) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Change in Tumor Necrosis Factor-alpha (TNF-α) from Baseline to Day 14
Time frame: From baseline through Day 14, assessed on Days 0 and 14
Number of days of organ function support (vasopressors, mechanical ventilation, or renal replacement therapy)
Time frame: From randomization to hospital discharge or through study completion, an average of approximately 22 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Li Ma, MD, PhD study director
Emergency Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-dose safflower granules and Medium-dose safflower granules in people with Sepsis and Disseminated Intravascular Coagulation (DIC), run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Li Ma, MD, PhD (+86-15921615410, Malipostgraduate2@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in SOFA score from baseline to Day 14 (time frame: From baseline (before the first dose) through Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.