Anakinra for Pediatric Multiple Organ Failure

(TRIPS Trial)

Recruiting at 34 trial locations

Overseen By Mark Hall, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Nationwide Children's Hospital

Must not be taking: Anakinra, GM-CSF

Disqualifiers: Myeloid leukemia, Pregnancy, Lactating, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well anakinra can help children with sepsis-induced multiple organ dysfunction syndrome (MODS) by reducing severe inflammation. MODS is a serious condition where different organs fail to function properly due to infection. The trial compares different doses of anakinra to determine the most effective, with some participants receiving a placebo for comparison. Children who have been in the ICU and developed at least two new organ problems due to an infection in the last few days might be suitable for this trial. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially life-saving advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that anakinra is generally well-tolerated in children. In one study, 41% of children with moderate to severe illness received anakinra and showed promising results. Another study examined children receiving doses similar to those in this trial (about 8 mg per kilogram per day) and found it safe and effective in reducing symptoms like fever and inflammation. Long-term safety data also supports anakinra's use, with most patients handling it well over time.

However, while most children do well on anakinra, rare serious events have occurred. For instance, one report mentioned a child who died due to complications from another condition while on anakinra. This underscores the importance of close monitoring during treatment.

Overall, existing evidence suggests that anakinra is a safe option for treating severe inflammation in children, but like all treatments, it may have some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Anakinra for pediatric multiple organ failure because it offers a unique approach by blocking the action of interleukin-1 (IL-1), a protein that plays a key role in inflammation. Unlike the standard treatments, which often focus on general inflammation reduction, Anakinra specifically targets IL-1, potentially leading to more effective management of inflammation with fewer side effects. Additionally, it is administered intravenously and can be adjusted to different dosages, allowing for a tailored approach based on the severity of the condition. This targeted mechanism and flexibility make Anakinra a promising option in managing this complex condition.

What evidence suggests that this trial's treatments could be effective for pediatric multiple organ failure?

Research has shown that anakinra, a medication that reduces inflammation, may help treat children with severe inflammation-related illnesses. In one study, 41% of children with a condition like sepsis were seriously ill, and anakinra was used successfully in these cases. Another study found that organ function improved, with eight out of nine children surviving until they left the hospital after receiving anakinra. These results suggest that anakinra could help manage severe inflammation and improve recovery in children with multiple organ problems caused by sepsis. Participants in this trial will receive different dosages of anakinra or a placebo to evaluate its effectiveness further. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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.

Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra
• Placebo

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.

How Is the Trial Designed?

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

Anakinra is already approved in European Union, United States for the following indications:

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

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]

Anakinra, an IL-1 receptor antagonist, has shown effectiveness in treating conditions like adult-onset Still's disease (AOSD), but it can also lead to serious side effects, such as acute liver failure.

This case report highlights the occurrence of severe acute liver failure in an adolescent male treated with anakinra, suggesting that while the drug is beneficial, careful monitoring for liver complications is essential, especially as its use expands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anakinra-Induced Acute Liver Failure in an Adolescent Patient with Still's Disease. Taylor, SA., Vittorio, JM., Martinez, M., et al.[2016]

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]

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 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]

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]

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]

Current pediatric guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) in children primarily recommend a serotonin 5-HT(3) receptor antagonist combined with a corticosteroid, but lack robust evidence and do not include many effective agents used in adults.

The review highlights the need for alternative antiemetic options for children who cannot tolerate or do not respond to standard treatments, discussing both established and emerging therapies like metopimazine, nabilone, and acupuncture, which may offer additional relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing emetic control in children receiving antineoplastic therapy: beyond the guidelines. Dupuis, LL., Nathan, PC.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10666339/

Impact of anakinra use on clinical outcomes in children ... Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra ...

2. pediatricsnationwide.org pediatricsnationwide.org/2019/04/19/targeting-therapies-for-children-with-multiple-organ-dysfunction/

Targeting Therapies for Children With Multiple Organ ... The scores suggest organ function improvements. Eight out of nine children survived to hospital discharge.

3. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42495

Variation in Early Anakinra Use and Short‐Term Outcomes in ... Despite empiric use of cytokine inhibitors in the management of MIS-C, there remains little data on their effectiveness to define optimal use, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10388456/

Clinical outcomes and safety of anakinra in the treatment ... Our findings reveal favorable clinical outcomes associated with treatment of MIS-C patients with adjunctive anakinra, suggesting that anakinra ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00069329

Study Details | NCT00069329 | Anakinra to Treat Patients ... This study will evaluate the safety and effectiveness of anakinra (Kineret) for treating patients with neonatal-onset multisystem inflammatory disease (NOMID)

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03932344

Long-term Safety Study of Kineret® in Patients With ... This is an international, non-interventional, single-armed, pharmacovigilance registry study on long-term safety of Kineret utilizing already available data ...

7. link.springer.com link.springer.com/article/10.1007/s40272-025-00712-7

Long-Term Safety of Anti-Interleukin-1 Medications in ... One patient died owing to MAS while on treatment with anakinra; two patients died after discontinuing anakinra, one due to multiorgan failure ...

8. ped-rheum.biomedcentral.com ped-rheum.biomedcentral.com/counter/pdf/10.1186/s12969-023-00924-6.pdf?utm_source=consensus

Impact of anakinra use on clinical outcomes in children ... A phase II open-label study demonstrated safe use of anakinra in resistant KD and its effect on reducing fever, inflammatory markers, and ...