Anakinra for Pediatric Multiple Organ Failure

(TRIPS Trial)

Recruiting at27 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Nationwide Children's Hospital

Must not be taking: Anakinra, GM-CSF

Disqualifiers: Myeloid leukemia, Pregnancy, Lactating, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests anakinra, a drug that reduces inflammation, in children with severe inflammation due to sepsis-induced organ failure. Anakinra works by blocking a protein that causes inflammation. It is widely used in treating Rheumatoid Arthritis and has shown potential in managing hyperinflammatory conditions like sepsis.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have taken anakinra or GM-CSF in the last 28 days, you cannot participate.

Is Anakinra safe for children?

Anakinra is generally used for various inflammatory conditions, but it can have side effects like injection site reactions and increased risk of infections. Rarely, it may cause liver problems, as seen in some children with certain diseases, so monitoring is important. ^{1 2 3 4 5}

How is the drug Anakinra unique for treating pediatric multiple organ failure?

Anakinra is unique because it targets the interleukin-1 (IL-1) pathway, which is involved in inflammation, making it different from other treatments that may not specifically address this pathway. This approach can be particularly beneficial in conditions where inflammation plays a key role, such as multiple organ failure. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

This trial is for children from newborns up to 17 years old with severe inflammation due to sepsis-induced organ failure. They must have had a recent worsening in organ function and suspected or confirmed infection causing it. Kids can't join if they're under 3kg, pregnant, lactating, have certain blood disorders or immune conditions, are likely to die within 48 hours, or previously received specific treatments.

Inclusion Criteria

Admission to the PICU or CICU

I have or might have an infection that led to my multiple organ dysfunction syndrome.

I am older than 40 weeks corrected gestational age but younger than 18 years.

Exclusion Criteria

My white blood cell count is low due to recent intense therapy.

My weight is less than 3 kilograms.

I have a history of blood disorders like leukemia or low platelet counts due to an autoimmune condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 days

Treatment

Participants receive intravenous (IV) anakinra or placebo for 7 days

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Long-term follow-up

Assessment of health-related quality of life and functional status

3 months

Treatment Details

Interventions

• Anakinra (Interleukin-1 Receptor Antagonist)
• Placebo (Other)

Trial Overview The TRIPS study tests the drug Anakinra against a placebo in kids with sepsis-induced multiple organ dysfunction syndrome (MODS). It's a double-blind trial meaning neither doctors nor patients know who gets the real drug versus the placebo. The goal is to see if Anakinra can reverse severe inflammation.

Participant Groups

Group I: Anakinra 16 mg/kg/day Active Control 1 Intervention

IV Anakinra 16 mg/kg/day x 7 days

Group II: Anakinra 8 mg/kg/day Active Control 1 Intervention

IV Anakinra 8 mg/kg/day x 7 days

Group III: Anakinra 12 mg/kg/day Active Control 1 Intervention

IV Anakinra 12 mg/kg/day x 7 days

Group IV: Anakinra 4 mg/kg/day Active Control 1 Intervention

IV Anakinra 4mg/kg/day x 7 days

Group V: Placebo Placebo Group 1 Intervention

IV placebo x 7 days

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Catherine Krawczeski

Nationwide Children's Hospital

Chief Medical Officer

MD

Timothy C. Robinson

Nationwide Children's Hospital

Chief Executive Officer since 2019

BSc in Psychology and Business Administration from Indiana University

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Dr. Diana W. Bianchi

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Executive Officer since 2016

MD from Stanford University

Dr. Alison Cernich

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Medical Officer since 2020

PhD in Clinical Psychology from University of Maryland

Findings from Research

Anakinra, an IL-1 receptor antagonist used for conditions like systemic juvenile idiopathic arthritis and Kawasaki disease, has been associated with rare cases of hepatotoxicity in pediatric patients, as demonstrated in a case series of three children.

The hepatotoxicity observed in these patients occurred after treatment with anakinra for severe macrophage activation syndrome, highlighting the need for careful monitoring of liver function during treatment with this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anakinra and hepatotoxicity in pediatric rheumatology: a case series. Martins, FR., Azevedo, AC., Ganhão, S., et al.[2023]

Anakinra, a biological drug used for rheumatoid arthritis and autoinflammatory diseases, effectively induced remission in a 28-year-old man with familial Mediterranean fever.

While anakinra was effective for the patient's autoinflammatory condition, it also coincided with a flare-up of his ulcerative colitis, highlighting the need for careful monitoring of patients with multiple conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ulcerative Colitis and Familial Mediterranean Fever: Can Anakinra Treat Both? Kaly, L., Rozenbaum, M., Rimar, D., et al.[2020]

In a retrospective study of 22 pediatric patients with undifferentiated autoinflammatory disease (uAID), 72% responded positively to anakinra, with 36% achieving complete clinical and serological remission within 3 months of treatment.

Anakinra was generally well tolerated, with no new safety concerns identified, although there were serious adverse events including 3 deaths (14%) and 1 case of allogeneic stem cell transplantation (5%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of anakinra for undifferentiated autoinflammatory diseases in children: a retrospective case review. Garg, S., Wynne, K., Omoyinmi, E., et al.[2022]

In a study of 82 pediatric patients with refractory multisystemic inflammatory syndrome in children (MIS-C), treatment with anakinra led to significant clinical improvements, with 89.1% of patients discharged without any lasting health issues.

Anakinra was found to be safe for most patients, with no injection site reactions reported; however, elevated liver enzymes were noted in some patients, and there were a few serious cases, including 1.8% mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. Çaǧlayan, Ş., Sönmez, HE., Otar Yener, G., et al.[2022]

A retrospective review of 26 pediatric patients showed that aprepitant and fosaprepitant, used for preventing chemotherapy-induced nausea and vomiting, were well tolerated with no reported adverse effects.

This study highlights the successful use of aprepitant in very young patients, including those as young as 11 months, expanding the potential age range for this treatment in children undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant and fosaprepitant use in children and adolescents at an academic medical center. Shillingburg, A., Biondo, L.[2021]

In a phase 3 trial involving 307 pediatric patients aged 6 months to 17 years, aprepitant significantly improved the prevention of chemotherapy-induced nausea and vomiting, with 51% of patients achieving a complete response compared to 26% in the control group (p<0.0001).

The safety profile of aprepitant was comparable to the control, with the most common serious adverse events being febrile neutropenia, indicating that aprepitant can be safely used in combination with ondansetron for children undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Kang, HJ., Loftus, S., Taylor, A., et al.[2018]

A single dose of intravenous fosaprepitant (150 mg) is as effective as a 3-day oral regimen of aprepitant in preventing chemotherapy-induced nausea and vomiting (CINV) when combined with ondansetron and dexamethasone, based on a study involving 2,247 patients.

Both treatment regimens were well tolerated, but fosaprepitant had a higher incidence of infusion site reactions compared to aprepitant (2.7% vs. 0.3%), indicating a potential safety consideration when choosing between the two options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. Grunberg, S., Chua, D., Maru, A., et al.[2022]

Aprepitant combined with ondansetron and dexamethasone (triple therapy) significantly reduces the risk of chemotherapy-induced vomiting in children and adolescents undergoing moderate to highly emetogenic chemotherapy, with a relative risk of 0.48 based on a review of three trials involving 451 patients.

The triple therapy did not increase the incidence of febrile neutropenia, indicating it is a safe option for managing nausea and vomiting during chemotherapy without adding additional risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant in pediatric patients using moderate and highly emetogenic protocols: a systematic review and meta-analyses of randomized controlled trials. Okumura, LM., D'Athayde Rodrigues, F., Ferreira, MAP., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Anakinra and hepatotoxicity in pediatric rheumatology: a case series. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Ulcerative Colitis and Familial Mediterranean Fever: Can Anakinra Treat Both? [2020]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of anakinra for undifferentiated autoinflammatory diseases in children: a retrospective case review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Anakinra-Induced Acute Liver Failure in an Adolescent Patient with Still's Disease. [2016]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Aprepitant and fosaprepitant use in children and adolescents at an academic medical center. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Aprepitant in pediatric patients using moderate and highly emetogenic protocols: a systematic review and meta-analyses of randomized controlled trials. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing emetic control in children receiving antineoplastic therapy: beyond the guidelines. [2021]