# AIRCHILL Pivotal Trial Detailed Cost Model & Benchmark Studies

> Detailed bottom-up cost model for the ~2,300-patient AIRCHILL cardiac-arrest pivotal trial with lean/base/high scenarios and comparison against TTM2, PRINCESS/PRINCESS2, EuroHYP-1, COTTIS-2/CUCUMBER and published medical…

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- Last modified: 2026-08-29T16:00:36+00:00

Finance model · version 1.0 · 29 August 2026

# Detailed AIRCHILL pivotal-trial cost model and benchmark studies.

A bottom-up planning model for the current ~2,300-patient cardiac-arrest pivotal concept. It shows where the money is expected to go, which assumptions dominate uncertainty, and why published grants from apparently similar cooling trials cannot be treated as complete trial costs. Every figure is labelled as sourced, derived or an AIRCHILL planning assumption.

Executive model

## Three cost scenarios for the same 2,300-patient trial.

Lean / investigator-led
€41.4m
€36.0m subtotal plus 15% contingency. Approx. €18,020 per randomised patient. Requires strong academic infrastructure, low site payments, highly efficient device deployment and substantial in-kind support.

Base / multinational EU
€78.6m
€68.4m subtotal plus 15% contingency. Approx. €34,190 per patient. This is the current P50-style management planning case.

High / commercial CRO
€159.4m
€132.8m subtotal plus 20% contingency. Approx. €69,287 per patient. Represents expensive CRO/site pricing, larger device fleet, slower recruitment and more US-like commercial execution.

Scope. These numbers are for the pivotal clinical programme and its investigational device fleet. They do not include the earlier engineering programme needed to reach design freeze, complete bench verification, large-animal validation and first-in-human airway safety. Those costs remain separately tracked in the AIRCHILL standards/regulatory cost matrix.

Bottom-up detail

## Base case: €68.38m before contingency, €78.64m including 15% reserve.

Cost blockLean €mBase €mHigh €mBase-case assumption / driver

Protocol, regulatory strategy & submissions1.502.504.00CIP/SAP/IB/ethics/competent-authority packages, amendments, country coordination

CRO / central project management2.504.508.00Programme office, vendors, sites, issue management across 24-month recruitment

EDC / database / data management1.502.504.00EDC build, validation, queries, device-data integration, database lock

Monitoring2.004.008.00Risk-based central + on-site monitoring across EMS/hospital networks

Statistics0.801.502.50Randomisation, interim, SAP, final analysis, regulatory outputs

DSMB / medical monitoring0.501.001.50Independent board, closed reports, safety review, adjudication

TMF / quality / audit0.801.502.50eTMF, sponsor QA, vendor qualification, audits, inspection readiness

Site / EMS activation2.004.5010.50Base assumes ~60 networks at blended €75k activation/contract/setup cost

Training & simulation1.003.005.00EMS/ED/ICU training, recertification, simulation and device competency

Screening burden1.503.005.00Screen failures, screening logs, emergency consent/documentation work

Randomised-patient site payments11.5017.2534.50Base: 2,300 × €7,500 blended EMS/hospital research payment

90-day follow-up0.691.382.30Base: 2,300 × ~€600 central/blinded neurological follow-up

AIRCHILL investigational device fleet5.2511.0022.50Lean ~700×€7.5k; base ~1,100×€10k; high ~1,200×€18.75k

Commissioning / installation / calibration0.501.323.00Vehicle integration, acceptance, initial calibration and deployment

Service / maintenance / replacement pool1.002.756.0024-month field service, swaps, calibration and repairs

Study consumables0.701.382.50Patient-side circuits, gas-path disposables and treatment-arm consumables

Logistics / warehousing0.601.503.00Inventory, shipment, returns and cross-border logistics

Clinical-trial insurance0.701.503.00Jurisdiction-specific participant/sponsor liability

Local regulatory / translations / legal0.400.802.00Local submissions, translations and contracts

Health economics / PROs0.300.701.50EQ-5D, resource-use dataset and economic analysis

Close-out / archiving / publication0.300.801.50Site closeout, archive, CSR/publication package

Subtotal36.0468.38132.80Before contingency

Contingency15%15%20%Recruitment, inflation, device replacement, amendments and vendor uncertainty

Total41.4578.64159.36Current management planning range

What drives the budget

## Four variables dominate AIRCHILL trial economics.

1 · Enrolment per device

### Fleet efficiency

Moving from near-fleet-wide coverage to targeted high-volume dispatch can remove hundreds of study devices and the associated training, service and logistics burden.

2 · Site payment

### €5k vs €15k per randomised patient

Across 2,300 patients, each €1,000 change in the blended research payment moves total cash cost by €2.3m before contingency.

3 · Recruitment duration

### Two years versus four

Slow recruitment extends CRO, monitoring, service, insurance, training-refresh and project-management costs even if the statistical sample size does not change.

4 · Outsourcing model

### Academic network versus commercial CRO

Existing academic infrastructure and in-kind services can make the cash budget look dramatically lower without making the true economic resource use disappear.

Comparable cooling trials

## Published budgets are not directly comparable — so the table shows what each number actually means.

Study / programmeTarget / actual NPublished moneyWhat the number representsApprox. ratioLesson for AIRCHILL

TTM21,900 randomisedAUD 3,247,977 + 463,957 + 154,652 + 154,652 = AUD 4.021mNamed public/research grants listed by ANZICS; not a complete economic trial-cost statement. Routine hospital infrastructure and in-kind resource use are not monetised in this figure.~AUD 2,116 / patient in listed grantsLarge pragmatic academic RCTs can run with relatively low visible grant cash when existing ICU/research infrastructure absorbs major resource use.

PRINCESS677 randomisedGrant amounts not publicly itemised in the paperFunded by Swedish Heart-Lung Foundation and Laerdal Foundation; cooling devices were supplied by BrainCool at no cost.Not calculableFree devices and manufacturer support materially reduce the sponsor cash requirement; AIRCHILL must explicitly value its RTW fleet instead of treating hardware as free.

PRINCESS21,022 target; first 100-patient pilot publishedNamed Swedish Heart-Lung Foundation, Region Stockholm and Laerdal grants; full trial budget not publicly disclosedPublications disclose funders/grant numbers, not a complete trial budget.Not calculableOperational pilot-before-pivotal design is directly relevant; financing cannot be benchmarked from grant acknowledgements alone.

EuroHYP-11,500 planned; 98 enrolled€11.741m total project cost; €8.082m EU contributionCORDIS total project budget covering a broad European phase-III hypothermia programme and supporting project activities.€7,827 per intended patient; €119,804 per actual enrollee if total project budget is divided by 98 — not a true per-patient costThe key warning: insufficient recruitment can destroy the economics. EuroHYP-1 stopped because of slow recruitment and cessation of funding despite a substantial budget.

CUCUMBER / COTTIS-2COTTIS-2 target 400€3.759m total H2020 project cost; €2.936m EU contributionEU project covers product development/market preparation and the COTTIS programme, not a pure trial-only invoice.~€9,398 per targeted COTTIS-2 patient if naively divided by 400Useful EU device-plus-trial benchmark, but the numerator contains non-trial work; it therefore cannot be used as a direct site-cost estimate.

US complex therapeutic-device benchmarkModelled pivotal study mean n=565US$54,332 per pivotal patient in 2018 dollarsPublished Medidata-based per-patient model for complex therapeutic device pivotal studies; study model estimated ~US$30.7m out-of-pocket for the pivotal phase.US$54,332 / patientAIRCHILL base case (~€34k/patient including device fleet and central overhead) sits below this US complex-device benchmark; the high case (~€69k/patient) is above it.

Do not rank studies by “cost per patient” without reading the denominator and cost scope. TTM2 reports grants, EuroHYP and CUCUMBER report total EU-project economics, PRINCESS includes free manufacturer-supplied hardware, and the JAMA model is a commercial US device-development benchmark. AIRCHILL therefore uses its own bottom-up resource model rather than copying a single external cost-per-patient number.

From EuroHYP-1 to COTTIS-2

## Evolution of the European cooling strategy.

There is no verified formal trial called “EuroHYP-2” in the sources used for this evidence register. The scientifically relevant development line is better described as EuroHYP-1 → COTTIS-2: EuroHYP-1 tested systemic hypothermia in a broad acute-ischaemic-stroke population, while COTTIS-2 moves the cooling intervention into a more selected large-vessel-occlusion population undergoing endovascular thrombectomy.

What EuroHYP-1 taught: the study planned 1,500 patients but enrolled only 98 and stopped after slow recruitment and cessation of funding. Its reports describe substantial organisational and logistical burden from delivering prolonged hypothermia in routine stroke care. For AIRCHILL, this means that treatment complexity, shivering management, staff workload, eligibility and enrolment speed are not secondary operational issues — they are determinants of whether a pivotal trial can finish at all.

What COTTIS-2 changes: the modern strategy concentrates on patients with large-vessel occlusion who are already undergoing thrombectomy, with cooling initiated very early around the reperfusion window. This creates a more mechanistically enriched population and avoids designing the first efficacy trial around prolonged cooling of a broad group of awake stroke patients. The CUCUMBER/COTTIS-2 programme therefore represents a more relevant contemporary European comparator for AIRCHILL-STROKE than EuroHYP-1 alone.

Why AIRCHILL-STROKE is closer to COTTIS-2: the current AIRCHILL protocol also targets selected LVO patients undergoing EVT who require general anaesthesia and invasive ventilation for clinical reasons. AIRCHILL is intended to start after airway control and as early as feasible before or during thrombectomy, with a hard requirement that study treatment must not delay arterial puncture or reperfusion. The route differs — respiratory cooling rather than transnasal plus surface cooling — but the trial-design logic is similar: earlier peri-reperfusion neuroprotection in a selected, already instrumented population.

Remaining lesson from COTTIS-2: even a focused EVT trial can face site-activation, contracting and protocol-adherence problems. AIRCHILL should therefore complete a multicentre run-in, measure eligible patients and randomisations per centre-month, and prove that cooling can be delivered without delaying reperfusion before locking the pivotal network and budget.

Source register

## Primary sources used in this comparison.

TTM2: ANZICS study page lists sample size 1,900 and the four named funding amounts. [Source →](https://www.anzics.org/current-active-endorsed-research/ttm2-trial/)

PRINCESS: JAMA/PMC publication reports 677 randomised patients, independent grant funding and that BrainCool supplied study devices without charge. [Source →](https://pmc.ncbi.nlm.nih.gov/articles/PMC6506882/)

PRINCESS2: 2026 pilot publication reports the first 100 participants of the ongoing 1,022-patient trial and names funding sources. [Source →](https://pmc.ncbi.nlm.nih.gov/articles/PMC12930594/)

EuroHYP-1: European Commission CORDIS reports €11,740,832.37 total cost and €8,081,665.40 EU contribution. The final trial report and registry document 98 of 1,500 planned patients and termination after slow recruitment/funding cessation. [CORDIS →](https://cordis.europa.eu/project/id/278709/results) · [Registry →](https://clinicaltrials.gov/study/NCT01833312)

CUCUMBER / COTTIS-2: CORDIS reports €3,759,322.50 total project cost and €2,936,494 EU contribution; COTTIS-2 is designed for 400 patients. This programme is treated here as the practical European successor strategy to EuroHYP-1 — not as a trial formally named “EuroHYP-2”. [CORDIS →](https://cordis.europa.eu/project/id/958809) · [COTTIS-2 →](https://www.cottis2trial.org/)

Complex medical-device benchmark: Sertkaya et al., JAMA Network Open 2022, reported a pivotal-study cost parameter of US$54,332 per patient in 2018 dollars and a mean pivotal sample of 565. [Source →](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796179)

AIRCHILL figures: All site-payment, device-unit-cost, staffing, CRO and contingency values are management assumptions until replaced by quotations. [RTW deployment model →](https://www.medicalcooling.com/airchill-cardiac-arrest-trial-budget-rtw-deployment/) · [Cardiac-arrest CIP →](https://www.medicalcooling.com/cip-airchill-cardiac-arrest/) · [Clinical Investigation Package →](https://www.medicalcooling.com/airchill-clinical-investigation-package/)