Study Design of the Diacerein in Patients With Covid-19

NCT05226754 | Unknown Phase 2 DMC

• 1 other identifier: 50440921.6.0000.5404
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, placebo-controlled, double-blind trial pilot study. This study will include individuals over 18 years of age who have been hospitalized with a confirmed diagnosis of COVID-19 to assess whether DIACEREIN treatment is safe and effective in controlling or decreasing inflammation in the body and viral load (amount of virus in the body in these patients).

Conditions

COVID-19

Keywords

COVID-19; Diacerein; Inflammatory Cytokine; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Serum levels of cytokines, troponin-T and D-dimer

  The endpoints are the change in the serum levels of cytokines, troponin-T and D-dimer from Day 0 to Day 5 of hospitalization, and from Day 0 to Day 10, as well as the area under the curve considering all measurements from Day 0 to Day 10.

  Day 0, Day 2, Day 5, Day 10

Secondary Outcomes (3)

• Time to clinical deterioration

  Day 0 to Day 10

• Adverse events

  Day 0 to Day 10

• Severe adverse events

  Day 0 to Day 10

Study Arms (2)

GROUP A

ACTIVE COMPARATOR

diacerein 50 mg (capsules) every 12 hours for 10 days

Drug: Diacerein

GROUP B

PLACEBO COMPARATOR

placebo capsules (lactose and magnesium stearate)

Drug: placebo capsules

Interventions

Diacerein DRUG

After enrolment, patients will be randomized (n=20 group A) to receive diacerein capsules 50 mg every 12 hours for 10 days.

Also known as: Artrodar®-capsules 50mg

GROUP A

placebo capsules DRUG

After enrolment, patients will be randomized (n=20 group A) to receive placebo capsules (lactose and magnesium stearate) every 12 hours for 10 days.

Also known as: lactose and magnesium stearate

GROUP B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients of either sex (≥18 years of age) with a diagnosis of COVID-19 infection, confirmed by positive polymerase chain reaction PCR reaction.
• Patient or his/her legal representative provide written informed consent prior to the start of the study.

You may not qualify if:

• Patients already hospitalized and on mechanical ventilation for over 48 hours;
• Pregnant or breastfeeding women;
• Contraindication for the use of diacerein or history of diacerein hypersensitivity;
• End-stage renal disease requiring renal replacement therapy;
• Chronic liver disease and/or ALT and AST ≥5 times the normal upper reference limit;
• Any active underlying malignancy;
• Currently enrolled in another research study;
• Peripheral capillary oxygen saturation/fraction of inspired oxygen ratio \<100;
• Use of high dose of \>1.0 mcg/kg/min of norepinephrine or need for rescue therapy with vasopressin;
• Bacterial or fungal infection, except for mild cutaneous infection or sinus infection.
• Any condition which, in the opinion of the Investigator, places the patient at unacceptable risk if they were to participate in the study;
• Clinically relevant serious co-morbid medical conditions including, but not limited to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, severe hepatic impairment, active central nervous system (CNS) disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV), active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements;
• Treatment with any immunosuppressive therapy other than corticosteroids within 30 days prior to Screening;

Sponsors & Collaborators

• University of Campinas, Brazil: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (2)

Unicamp Clinical Hospital

Campinas, São Paulo, 13083-888, Brazil

RECRUITING

Hospital Estadual Sumaré

Sumaré, São Paulo, 13175-490, Brazil

RECRUITING

Related Publications (16)

• Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020 Jun;20(6):363-374. doi: 10.1038/s41577-020-0311-8. Epub 2020 Apr 28.

  PMID: 32346093 RESULT

• RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17.

  PMID: 32678530 RESULT

• Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 Feb 15;395(10223):473-475. doi: 10.1016/S0140-6736(20)30317-2. Epub 2020 Feb 7. No abstract available.

  PMID: 32043983 RESULT

• Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, Criner GJ, Kaplan-Lewis E, Baden R, Pandit L, Cameron ML, Garcia-Diaz J, Chavez V, Mekebeb-Reuter M, Lima de Menezes F, Shah R, Gonzalez-Lara MF, Assman B, Freedman J, Mohan SV. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jan 7;384(1):20-30. doi: 10.1056/NEJMoa2030340. Epub 2020 Dec 17.

  PMID: 33332779 RESULT

• de Oliveira PG, Termini L, Durigon EL, Lepique AP, Sposito AC, Boccardo E. Diacerein: A potential multi-target therapeutic drug for COVID-19. Med Hypotheses. 2020 Nov;144:109920. doi: 10.1016/j.mehy.2020.109920. Epub 2020 Jun 1.

  PMID: 32534337 RESULT

• 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.

  PMID: 22870441 RESULT

• Yang L, Li J, Xu L, Lin S, Xiang Y, Dai X, Liang G, Huang X, Zhu J, Zhao C. Rhein shows potent efficacy against non-small-cell lung cancer through inhibiting the STAT3 pathway. Cancer Manag Res. 2019 Feb 1;11:1167-1176. doi: 10.2147/CMAR.S171517. eCollection 2019.

  PMID: 30774444 RESULT

• Yang Y, Peng F, Wang R, Yange M, Guan K, Jiang T, Xu G, Sun J, Chang C. The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. J Autoimmun. 2020 May;109:102434. doi: 10.1016/j.jaut.2020.102434. Epub 2020 Mar 3.

  PMID: 32143990 RESULT

• Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020 Jun 16;11:1446. doi: 10.3389/fimmu.2020.01446. eCollection 2020.

  PMID: 32612617 RESULT

• Singh A, Strobbe D, Campanella M. Pyroptosis targeting via mitochondria: An educated guess to innovate COVID-19 therapies. Br J Pharmacol. 2022 May;179(10):2081-2085. doi: 10.1111/bph.15670. Epub 2021 Oct 10.

  PMID: 34632567 RESULT

• Ferreira AC, Soares VC, de Azevedo-Quintanilha IG, Dias SDSG, Fintelman-Rodrigues N, Sacramento CQ, Mattos M, de Freitas CS, Temerozo JR, Teixeira L, Damaceno Hottz E, Barreto EA, Pao CRR, Palhinha L, Miranda M, Bou-Habib DC, Bozza FA, Bozza PT, Souza TML. SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes. Cell Death Discov. 2021 Mar 1;7(1):43. doi: 10.1038/s41420-021-00428-w.

  PMID: 33649297 RESULT

• Rodrigues TS, de Sa KSG, Ishimoto AY, Becerra A, Oliveira S, Almeida L, Goncalves AV, Perucello DB, Andrade WA, Castro R, Veras FP, Toller-Kawahisa JE, Nascimento DC, de Lima MHF, Silva CMS, Caetite DB, Martins RB, Castro IA, Pontelli MC, de Barros FC, do Amaral NB, Giannini MC, Bonjorno LP, Lopes MIF, Santana RC, Vilar FC, Auxiliadora-Martins M, Luppino-Assad R, de Almeida SCL, de Oliveira FR, Batah SS, Siyuan L, Benatti MN, Cunha TM, Alves-Filho JC, Cunha FQ, Cunha LD, Frantz FG, Kohlsdorf T, Fabro AT, Arruda E, de Oliveira RDR, Louzada-Junior P, Zamboni DS. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med. 2021 Mar 1;218(3):e20201707. doi: 10.1084/jem.20201707.

  PMID: 33231615 RESULT

• Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol. 2021 Nov;21(11):694-703. doi: 10.1038/s41577-021-00588-x. Epub 2021 Aug 9.

  PMID: 34373622 RESULT

• Fidelix TS, Macedo CR, Maxwell LJ, Fernandes Moca Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2014 Feb 10;2014(2):CD005117. doi: 10.1002/14651858.CD005117.pub3.

  PMID: 24515444 RESULT

• Huang M, Zong S-l and Zhang Q-y. The effect of food intake on the pk of rhein released from diacerein. Brazilian Journal of Pharmaceutical Sciences. 2020;56.

  RESULT

• Honvo G, Reginster JY, Rabenda V, Geerinck A, Mkinsi O, Charles A, Rizzoli R, Cooper C, Avouac B, Bruyere O. Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging. 2019 Apr;36(Suppl 1):65-99. doi: 10.1007/s40266-019-00662-z.

  PMID: 31073924 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

diacerein; Lactose; stearic acid

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Andrei C Sposito, MD.PHD

  State University of Campinas, Campinas, Brazil

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alejandro R Castillo, MD.PHD

CONTACT

+55 (19) 35219580; aleroselldr@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Brazilian Heart Study Group

Model Details: After enrolment, patients will be randomized (n=20 per group) 1:1 to receive either diacerein 50 mg or placebo treatment every 12 hours for 10 days. The research electronic data capture (REDCap) platform will be used as a randomization system. Patients, investigators and other support staff will be blinded to the experimental therapy. The study drug, diacerein (Artrodar®-capsules 50mg) and placebo capsules (lactose and magnesium stearate), will be similar in size and appearance to maintain blinding. All laboratory analyses will be performed blinded to the treatment. Identification of the study drug will only occur after locking the dataset.

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 7, 2022
• Study Start: April 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: July 8, 2023
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2)