Clinical Trial of Huoluo Pills Combined With Iguratimod Tablets in the Treatment of Rheumatoid Arthritis

Official title

A Multicenter Clinical Randomized Controlled Trial on the Efficacy and Safety of Huoluo Pills Combined With Iguratimod Tablets in the Treatment of Rheumatoid Arthritis

Overview

This study aims to systematically evaluate the efficacy and safety of Huoluo Pills combined with Iguratimod Tablets in the treatment of rheumatoid arthritis (RA). A total of 240 patients with RA belonging to the syndromes of Wind - Damp Obstruction or Cold - Damp Obstruction will be enrolled in 8 centers (randomly assigned to groups). The experimental group will receive oral Huoluo Pills combined with Iguratimod Tablets, while the control group will receive oral Iguratimod Tablets alone. Both groups will be administered continuously for 12 weeks. Primary Efficacy Index: The proportion of ACR20 responders in each group at the end of treatment. Key Secondary Efficacy Index: The change in DAS28 (CRP) score from baseline in each group at the end of treatment. Other Secondary Efficacy Indexes: RF, CRP, ESR, IL - 6, ACR50, ACR70, CDAI, SDAI, HAQ - DI, SF - 36, FACIT - Fatigue, and Traditional Chinese Medicine (TCM) syndrome scores. Safety Indexes: Physical examination, blood routine, urine routine, blood biochemistry, coagulation function, etc. This study will investigate the efficacy and safety of Huoluo Pills combined with Iguratimod Tablets in the treatment of RA with Wind - Damp Obstruction or Cold - Damp Obstruction syndromes.

Interventions

• Drug Huoluo Pills
  Huoluo Pills: Orally take 1 pill once, twice a day (swallow with warm water)
• Drug Iguratimod Tablets
  Iguratimod Tablets: Orally take 1 tablet once, twice a day (one tablet in the morning and one in the evening, after meals)

Primary outcome measures

• The proportion of subjects achieving ACR20 [Time frame: At the end of the treatment (on the 84th day)]

Secondary outcome measures (12)

• The change of Disease Activity Score in 28 Joints-C-Reactive Protein（DAS28-CRP） score compared with the baseline [Time frame: At the end of the treatment (on the 84th day)]
• The proportion of subjects achieving ACR20 [Time frame: By the 28th day of treatment]
• The change of Disease Activity Score in 28 Joints-C-Reactive Protein（DAS28-CRP） score compared with the baseline [Time frame: By the 28th day of treatment]
• The remission rate of Disease Activity Score in 28 Joints-C-Reactive Protein（DAS28-CRP） [Time frame: When treating up to the 28th and 84th days]
• The low activity rate of Disease Activity Score in 28 Joints-C-Reactive Protein（DAS28-CRP） [Time frame: When treating up to the 28th and 84th days]
• The remission rate of Disease Activity Score in 28 Joints-Erythrocyte Sedimentation Rate（DAS28-ESR） [Time frame: When treating up to the 28th and 84th days]
• The low activity rate of Disease Activity Score in 28 Joints-Erythrocyte Sedimentation Rate（DAS28-ESR） [Time frame: When treating up to the 28th and 84th days]
• The change of Disease Activity Score in 28 Joints-Erythrocyte Sedimentation Rate（DAS28-ESR） score compared with the baseline [Time frame: When treating up to the 28th and 84th days]
• The proportion of subjects with ACR50 [Time frame: When treating up to the 28th and 84th days]
• The proportion of subjects with ACR70 [Time frame: When treating up to the 28th and 84th days]
• The proportion of subjects with a CDAI（Clinical Disease Activity Index） score ≤ 10 [Time frame: When treating up to the 28th and 84th days]
• The proportion of subjects with a CDAI（Clinical Disease Activity Index） score ≤ 2.8 [Time frame: When treating up to the 28th and 84th days]

Eligibility criteria

Inclusion criteria

• Subjects who meet the Western medicine classification criteria for rheumatoid arthritis (RA) launched by the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) in 2010 and have been clearly diagnosed with RA.
• Subjects who meet the diagnostic criteria for traditional Chinese medicine syndromes of "Wind-Dampness Obstruction Syndrome (Main symptoms: ① Joint pain and swelling wandering; ② Joint pain and swelling intermittent. Secondary symptoms: ① Aversion to wind or sweating; ② Headache; ③ Heaviness of the limbs. Tongue and pulse manifestations: Pale red tongue thin white coating slippery or floating pulse. Diagnosis can be made by having 2 main symptoms or 1 main symptom + 2 secondary symptoms combined with the tongue and pulse manifestations)" or "Cold-Dampness Obstruction Syndrome (Main symptoms: ① Cold joint pain the joints feel cold to the touch and the skin color is not red; ② The pain worsens when exposed to cold and alleviates when warmed. Secondary symptoms: ① Joint stiffness limited flexion and extension; ② Cold limbs or aversion to cold and preference for warmth; ③ Bland taste in the mouth without thirst. Tongue and pulse manifestations: Enlarged tongue body pale tongue white or greasy coating wiry or tight pulse. Diagnosis can be made by having 2 main symptoms or 1 main symptom + 2 secondary symptoms combined with the tongue and pulse manifestations)".
• Subjects with a Disease Activity Score in 28 joints (DAS28) (ESR) score > 2.6 and ≤ 5.1 or a DAS28 (CRP) score > 2.3 and ≤ 4.1.
• Male or female subjects aged ≥ 18 years old and ≤ 70 years old.
• Subjects who have not used iguratimod and Huoluo Pills within 4 weeks before the first administration of the investigational drug.
• If the subject is receiving treatment with traditional disease-modifying antirheumatic drugs (DMARDs) during screening monotherapy with one of methotrexate (MTX) leflunomide or hydroxychloroquine is allowed and the dosage should be stable for at least 12 weeks before the first administration of the investigational drug (MTX dosage ≤ 15 mg/week leflunomide ≤ 20 mg/day hydroxychloroquine ≤ 400 mg/day).
• Subjects who are receiving treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during screening should have a stable dosage for at least 2 weeks before the first administration of the investigational drug and maintain the same dosage during the trial.
• Subjects who are receiving hormone treatment during screening should have a stable condition (limited to oral administration of ≤ 10 mg/d prednisone acetate or equivalent dose) for at least 4 weeks before the first administration of the investigational drug and maintain stable treatment during the trial.
• Subjects who voluntarily agree to participate in this trial sign a written informed consent form are able to follow the visit and related procedures specified in the protocol and have good compliance.

Exclusion criteria

• Those who have used plant medicine preparations such as Tripterygium glycosides total glucosides of paeony sinomenine or other traditional Chinese medicine preparations that affect the evaluation of the therapeutic effect within 4 weeks before the first administration of the test drug;
• Those who have received intramuscular injection intravenous injection or intra-articular injection of glucocorticoid treatment within 4 weeks before the first administration of the test drug;
• Patients who have received treatment with biological agents within 12 weeks before the first administration of the test drug;
• Those who suffer from active gastrointestinal diseases (such as peptic ulcers) severe interstitial lung diseases low bone marrow function severe cardiovascular and cerebrovascular diseases (such as acute myocardial infarction unstable angina pectoris intracerebral hemorrhage transient ischemic attack) severe organic lesions such as poorly controlled diabetes mellitus or those who have a history of malignant tumors in the past 5 years or those with mental illnesses. ;
• Those known to have tuberculosis HIV hepatitis B hepatitis C syphilis or other active or chronic persistent infections;
• Those who are allergic to the drugs involved in the research protocol or have contraindications to their use;
• Those who have received live vaccines within 4 weeks before screening or inactivated vaccines within 2 weeks before screening or those who have a vaccination plan during the trial;
• Those with any of the following conditions in the auxiliary examination during screening: 1) AST or ALT > 1.5 times the upper limit of the normal reference value or the estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m²; 2) Hemoglobin < 90 g/L or white blood cell count < 3.0×10⁹/L or neutrophil count < 1.5×10⁹/L or lymphocyte count < 0.5×10⁹/L or platelet count < 90×10⁹/L;
• Pregnant or lactating women those with a fertility plan or those planning to donate sperm or eggs;
• Those who are participating in other clinical trials before screening;
• Those whom the investigator deems to have other factors that make them unsuitable to participate in this trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07115641 · leadingpharm2025002 · ITMCTR2025000953 · MR-11-25-036909

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗