A study testing the medicine angiotensin II in patients of 0–17 years with a life-threateningly low blood pressure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Paion Pharma GmbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PAION Pharma GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effect of angiotensin II (AT2) versus placebo on the dose of standard-of-care (SOC) vasopressors, in paediatric patients with refractory hypotension in distributive shock receiving fluid resuscitation and SOC vasopressors

Secondary objectives 1

1. To (further) evaluate the effects of AT2 versus placebo on mean arterial pressure (MAP), the dose of SOC vasopressors, time until maintenance of IMP and dose at that time, and organ dysfunction in paediatric patients with refractory hypotension in distributive shock receiving fluid resuscitation and SOC vasopressors

Conditions and MedDRA coding

refractory hypotension in distributive shock

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001912-PIP02-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patient 0 to 17 years of age, any gender
2. Diagnosis of refractory hypotension in distributive (= vasodilatory) shock
3. Adequate fluid resuscitation at investigator’s discretion
4. Norepinephrine base equivalent dose > 0.2 µg/kg/min when checking inclusion criteria
5. Legal representative(s) signed informed consent and patient signed assent, per applicable regulatory requirement(s). If legal representative(s) are not available in this emergency situation, the investigator may still enrol the patient in the trial, in agreement with an independent physician. In this case, both the investigator and the independent physician need to sign a declaration of emergency enrolment. If the patient is sedated, unconscious, or unable to sign assent due to another cause, they can be enrolled without signed assent. In all cases, signed informed consent and/or signed assent must retrospectively be requested as soon as possible
6. Negative pregnancy test at screening for participants of childbearing potential, i.e. after menarche
7. Venous thromboembolism prophylaxis before beginning IMP administration if indicated per local guidelines

Exclusion criteria 12

1. At screening, preterm infants < 37 weeks of pregnancy and < 3.0 kg body weight at birth
2. Expected survival duration < 48 hours
3. Standing Do Not Resuscitate order
4. Acute coronary syndrome
5. Acute or history of mesenteric ischaemia
6. Acute or history of major bleeding in a critical area or organ within 30 days prior to randomisation
7. Active or history of venous or arterial thrombotic or thromboembolic events or previously diagnosed coagulopathy
8. Burns covering > 20% of total body surface area
9. Use of angiotensin receptor blocker within 48 hours prior to randomisation
10. Hypersensitivity to angiotensin II or to its excipients
11. Concurrent provision of breastfeeding
12. Current participation in another clinical trial with an investigational medicinal product not approved in that country

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the dose of SOC vasopressors, expressed as norepinephrine base equivalent dose (NED) sum/hour, from baseline to the first 6 hours of IMP

Secondary endpoints 6

1. Change in MAP as mean/h from baseline to the first 3 hours, 3–6, 6–12, 12–24, 24–48 hours
2. Change in the dose of SOC vasopressors, expressed as norepinephrine base equivalent dose (NED) sum/hour, from baseline to the first 3 hours, 3–6, 6–12, 12–24, 24–48 hours
3. Time from start of IMP administration to first maintenance dose sustained at the same dose for ≥ 1 hour, and the dose at that time
4. Change in paediatric logistic organ dysfunction (PELOD-2) score from baseline (all participants are at the PICU at baseline) to 48 hours (for participants who remain at the PICU at this time) and to day 7 (for participants who remain at the PICU at this time)
5. Change in blood lactate from baseline to 6, 12, 24 and 48 hours
6. Proportion of participants who achieve a ≥ 25%, ≥ 50% and ≥ 75% reduction in the dose of SOC vasopressors, expressed as NED sum/hour, from baseline to 6 hours, and who are alive, blinded to their treatment assignment, and have not been withdrawn at 6 hours

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Paion Pharma GmbH

Sponsor organisation

Paion Pharma GmbH

Address

Heussstrasse 25, Brand Brand

City

Aachen

Postcode

52078

Country

Germany

Scientific contact point

Organisation

Paion Pharma GmbH

Contact name

Carlijn Peerboom

Public contact point

Organisation

Paion Pharma GmbH

Contact name

Carlijn Peerboom

Third parties 2

Locations

4 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications