ANGIOTENSIN II for Distributive shock | Refractory hypotension

Inclusion criteria

• {"criterion_text":"- Patient 0 to 17 years of age, any gender\n- Diagnosis of refractory hypotension in distributive (= vasodilatory) shock\n- Adequate fluid resuscitation at investigator’s discretion\n- Norepinephrine base equivalent dose > 0.2 µg/kg/min when checking inclusion criteria\n- 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\n- Negative pregnancy test at screening for participants of childbearing potential, i.e. after menarche\n- Venous thromboembolism prophylaxis before beginning IMP administration if indicated per local guidelines"}

Exclusion criteria

• {"criterion_text":"- At screening, preterm infants < 37 weeks of pregnancy and < 3.0 kg body weight at birth\n- Expected survival duration < 48 hours\n- Standing Do Not Resuscitate order\n- Acute coronary syndrome\n- Acute or history of mesenteric ischaemia\n- Acute or history of major bleeding in a critical area or organ within 30 days prior to randomisation\n- Active or history of venous or arterial thrombotic or thromboembolic events or previously diagnosed coagulopathy\n- Burns covering > 20% of total body surface area\n- Use of angiotensin receptor blocker within 48 hours prior to randomisation\n- Hypersensitivity to angiotensin II or to its excipients\n- Concurrent provision of breastfeeding"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change expressed as norepinephrine base equivalent dose (NED) sum/hour from baseline to the first 6 hours of investigational medicinal product administration"}

Secondary endpoints

• {"endpoint_text":"- Change in MAP as mean/h from baseline to the first 3 hours, 3–6, 6–12, 12–24, 24–48 hours","definition_or_measurement_approach":"Change in mean arterial pressure (MAP) reported as mean per hour from baseline to specified time intervals (first 3 hours, 3–6, 6–12, 12–24, 24–48 hours)"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change expressed as NED sum/hour from baseline to specified time intervals (first 3 hours, 3–6, 6–12, 12–24, 24–48 hours)"}
• {"endpoint_text":"- Time from start of IMP administration to first maintenance dose sustained at the same dose for ≥ 1 hour, and the dose at that time","definition_or_measurement_approach":"Time interval from IMP start to first maintenance dose maintained for ≥1 hour; also record the maintenance dose at that time"}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Change in PELOD-2 score from baseline to 48 hours and to day 7 for participants remaining in PICU"}
• {"endpoint_text":"- Change in blood lactate from baseline to 6, 12, 24 and 48 hours","definition_or_measurement_approach":"Change in blood lactate measured at baseline and at 6, 12, 24 and 48 hours"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion achieving specified percentage reductions (≥25%, ≥50%, ≥75%) in NED sum/hour from baseline to 6 hours among those alive, still blinded and not withdrawn at 6 hours"}

Methods

• Site-based recruitment at participating paediatric intensive care units (PICUs) and paediatric critical care departments at listed hospital sites in France
• Site-based recruitment at participating paediatric intensive care units (PICUs) and paediatric departments at listed hospital sites in Germany
• Site-based recruitment at participating paediatric intensive care units at listed hospital site in Italy
• Site-based recruitment at participating paediatric intensive care and paediatric departments at listed hospital sites in Spain

France

Earliest CTIS Part Ii Submission Date

10-03-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

51

Number Of Sites

6

Number Of Participants

38

Germany

Earliest CTIS Part Ii Submission Date

25-04-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

5

Number Of Sites

3

Number Of Participants

45

Italy

Earliest CTIS Part Ii Submission Date

25-04-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

12

Number Of Sites

1

Number Of Participants

25

Spain

Earliest CTIS Part Ii Submission Date

25-04-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

12

Number Of Sites

7

Number Of Participants

35

Primary sponsor

Full Name

Paion Pharma GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Glatt Pharmaceutical Services GmbH & Co. KG","duties_or_roles":"sponsorDuties codes: 14; 15 (pack the vials into secondary packaging, label the Giapreza vials and secondary packaging with a compliant label, provide QP certification of the IMP finished product)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"AMS Advanced Medical Services GmbH","duties_or_roles":"sponsorDuties codes: 1, 11, 12, 2, 5, 6","organisation_type":"Pharmaceutical company"}