Clinical trial NCT03404479: Trial to Evaluate Efficacy and Safety of Combination of Diacerein and Celecoxib Administered in Patients With Knee OA
Official title: A Prospective, Randomized, Double-blinded, Multi-center, Trial to Evaluate Efficacy and Safety of Combination of Diacerein and Celecoxib Administered Orally in Patients With Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Knee Osteoarthritis
Keywords: Knee Osteoarthritis
Diacerein
Lead sponsor: Seoul St. Mary's Hospital
Sponsor class: OTHER
Collaborators: name: Korea University Guro Hospital
First posted: 2018-01-19
Enrollment: 90
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the pain relief effect of Co-administration of Diacerein with Celecoxib in patients with knee osteoarthritis compared with single administration of each drug.

Detailed description: A large epidemiological study in Europe reported that over four-thirds of patients with osteoarthritis received combination therapy with two or more drugs. Approximately 1.5% of patients with osteoarthritis using three or more drugs are using COX-2(Cyclo-oxygenase-2) inhibitors and SYSADOA(Symptomatic slow acting drug), And it has been investigated that much more patients are using the two classes of drugs when the range is extended to other oral NSAIDs other than COX-2 inhibitors. Therefore, considering the characteristics of patients with osteoarthritis, such as basal disease and treatment effects on each type of drug, it is important to find the optimal combination of drugs for each patient characteristics.

There is a previous study using osteoarthritis rat model as a biological basis of diacerein and celecoxib administration. Previous studies have shown that the combined use of Diacerein and Celecoxib improves osteoarthritis.

The purpose of this study is to evaluate the pain relief effect of Co-administration of Diacerein with Celecoxib in patients with knee osteoarthritis compared with single administration of each drug.

Eligibility criteria: Inclusion Criteria:

1. Subjects who voluntarily consented, after listening enough explanation for this study and investigational product.
2. Adult over 50 years of age.
3. At least one of the knee pain VAS score is 40mm or more.
4. Meets the ACR(American College of Rheumatology) criteria for diagnosis. (1) Confirmation of osteophytes on radiographic inspection. (2) One or more of the following three items.

   ① Age\> 50 years

   ② Morning stiffness \<30 minutes

   ③ Crepitus
5. Patients who require medication for more than 12 weeks due to osteoarthritis symptoms.
6. Those who are able to follow the requirements of this clinical trial, such as being able to trace during the clinical trial period and to read and write the VAS questionnaire.
7. Those who weigh more than 40kg

Exclusion Criteria:

1. Secondary knee osteoarthritis
2. Other inflammatory Knee Osteoarthritis (e.g. gout, rheumatoid arthritis, etc.)
3. Patients presenting with gastroesophageal reflux disease, peptic ulcer.
4. Helicobacter infected patients who have not been treated for eradication (recruitment if negative in re-examination after treatment).
5. Short bowel syndrome that can cause inflammatory bowel disease (ulcerative colitis, Crohn's disease) and drug absorption disorder.
6. Intestinal obstruction syndrome
7. Unexplained abdominal pain
8. ALT(Alanine aminotransferase) level of liver function test exceeded 5 times of reference range
9. Total bilirubin level exceeded 2 mg / dL
10. Serum albumin level less than 2 g / dL
11. Ascites
12. Hepatic encephalopathy
13. Hepatitis B, hepatitis C (excluding healthy carriers) or HIV positive
14. MDRD(Modification of Diet in Renal Disease) Estimated Glomerular filtration rate less than 60 mL / m2
15. Patients with hyperkalemia (over 5.5 meq / L)
16. history of asthma, acute rhinitis, nasal polyps, angioedema, urticaria or allergic reactions to aspirin or other non-steroidal anti-inflammatory drugs(including COX-2 inhibitors).
17. Malignant tumors other than basal cell or squamous cell carcinoma of the skin, CIN(Cervical Intraepitherial Neoplasia) and CIS(Carcinoma in situ) of the cervix, and intraepithelial carcinoma of other areas Within 5 years of consent date.
18. Medical history of hypersensitivity to the components of the investigational products. (The components of test drug 1 and 2, including the Rhein-based drug)
19. Patients with an allergic reaction to sulfonamide.
20. Patients with galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption.
21. Subjects who have not reached the prescribed period after receiving contraindicated medication or treatment before participation in this clinical trial.
22. Patients receiving contraindicated medication.
23. Alcohol and other drug abuse cases based on 6 months before screening.
24. Pregnant women or nursing mothers who are not willing to stop breastfeeding.
25. Female who do not fall into one or more of the following categories(In other words, only the following female can participate:)

    * (1) Menopause (non-therapy-induced amenorrhea of more than 12 months) Female
    * (2) Female infertility due to surgery (no ovaries and / or uterus)
    * (3) If you have sexual intercourse with only one male partner who has been confirmed to have no semen after fertilization.
    * (4) Female subjects who agreed to abstinence during the clinical trial period.
    * If the subject is assured of an abstinence throughout the trial period.(e.g. clergy)
    * However, intermittent abstinence (eg, contraception using ovulation period, symptothermal) or coitus interrupts is not a case of consent for abstinence.
    * (5) For women of childbearing age, the following methods or methods of contraception use the effective method of contraception to be used during the period of this clinical trial:
    * Oral contraceptive
    * The contraceptive patch
    * Intra uterine device (IUD)
    * contraceptive implant
    * contraceptive injection
    * intrauterine hormonal apparatus
    * Tubal ligation and infertility surgery
26. If 30 days have not elapsed after the date of signing of the previous clinical trial or currently participating in other clinical trials.
27. Patients who are scheduled for surgery during the clinical trial period or who have difficulties in completing the protocol during this clinical trial due to other reasons.
28. In addition to the above, other diseases that the investigator judges to be inappropriate.

Primary outcomes:
measure: pain VAS score
timeFrame: 12 weeks after randomization
Secondary outcomes:
measure: pain NRS score
timeFrame: 12 weeks after randomization
measure: WOMAC index score
timeFrame: 12 weeks after randomization
measure: GSRS index score
timeFrame: 12 weeks after randomization
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul ST. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: Seoul St. Mary's Hospital
name: Whan-Seok Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Guro Hospital
name: Seon-Mee Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li Z, Meng D, Li G, Xu J, Tian K, Li Y. Celecoxib Combined with Diacerein Effectively Alleviates Osteoarthritis in Rats via Regulating JNK and p38MAPK Signaling Pathways. Inflammation. 2015 Aug;38(4):1563-72. doi: 10.1007/s10753-015-0131-3.
citation: Martel-Pelletier J, Pelletier JP. Effects of diacerein at the molecular level in the osteoarthritis disease process. Ther Adv Musculoskelet Dis. 2010 Apr;2(2):95-104. doi: 10.1177/1759720X09359104.
citation: Panova E, Jones G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf. 2015 Mar;38(3):245-52. doi: 10.1007/s40264-015-0266-z.
citation: Nicolas P, Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. doi: 10.2165/00003088-199835050-00002.