Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

2023-507560-39-00 Protocol ATN-108 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 7 Jan 2025 · Status Ongoing, recruiting · 8 EU/EEA countries · 15 sites · Protocol ATN-108

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 142
Countries 8
Sites 15

Acquired Antithrombin Deficiency (Heparin Resistance)

The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin responsiveness in adult patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB)

Key facts

Sponsor
Octapharma AG
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
7 Jan 2025 → ongoing
Decision date (initial)
2024-08-05
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Octapharma AG

External identifiers

EU CT number
2023-507560-39-00
ClinicalTrials.gov
NCT06096116

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Dose response, Safety

The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin responsiveness in adult patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB)

Secondary objectives 10

  1. The amounts of further therapy containing antithrombin required for restoring heparin responsiveness before CPB and maintaining it during CPB
  2. The effect of Atenativ on the coagulation parameter used for evaluating heparin resistance, namely the activated clotting time (ACT)
  3. The capacity of Atenativ to modify the antithrombin plasma concentration
  4. The impact of Atenativ on the intraoperative use of heparin following the infusion of Atenativ or placebo
  5. Any requirement for frozen plasma (FP) or antithrombin concentrates for reasons other than restoring or maintaining heparin responsiveness, both intraoperatively and postoperatively
  6. Any intraoperative and postoperative use of other allogeneic blood products, coagulation factor concentrates and other haemostatic-relevant therapies
  7. The volume of chest tube drainage and the need for reoperation due to bleeding
  8. The safety of Atenativ
  9. Any post-CPB requirement for additional therapy containing antithrombin to restore heparin responsiveness
  10. The patient’s postoperative course, as assessed by length of intensive care unit (ICU) stay.

Conditions and MedDRA coding

Acquired Antithrombin Deficiency (Heparin Resistance)

VersionLevelCodeTermSystem organ class
20.0 PT 10074561 Acquired antithrombin III deficiency 100000004851
20.0 PT 10059598 Heparin resistance 100000004851

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Single period of study
Prospective, double-blind, three-arm, placebo-controlled, multicentre Phase 3 study
 Randomised Controlled Double [{"id":180780,"code":3,"name":"Monitor"},{"id":180781,"code":1,"name":"Subject"},{"id":180782,"code":4,"name":"Analyst"},{"id":180779,"code":2,"name":"Investigator"}] 1st cohort: One cohort will receive a single bolus of 15 international units (IU)/kg bodyweight (BW)
Atenativ
2nd cohort: second cohort will receive a single bolus of 30 IU/kg BW Atenativ
Placebo group: placebo group will receive a normal saline bolus

Regulatory references

Plan to share IPD
No
IPD plan description
N/A
EU CT numberTitleSponsor
2021-004307-40 A multicentre, prospective, open-label, uncontrolled Phase 3 study to assess the efficacy, safety and pharmacokinetics of Atenativ in patients with congenital antithrombin deficiency undergoing surgery or delivery , Étude prospective de phase 3, multicentrique, en ouvert, non contrôlée, visant à évaluer l’efficacité, la sécurité d’emploi et la pharmacocinétique d’Atenativ chez des patients atteints d’un déficit congénital en antithrombine nécessitant une intervention chirurgicale ou un accouchement, Studio multicentrico, prospettico, in aperto, non controllato, di fase 3 per valutare l’efficacia, la sicurezza e la farmacocinetica di Atenativ in pazienti con deficit congenito di antitrombina sottoposti ad intervento chirurgico o parto., Estudio en fase III, multicéntrico, prospectivo, sin enmascaramiento y no controlado para evaluar la eficacia, la seguridad y la farmacocinética de Atenativ en pacientes con deficiencia congénita de antitrombina que se someten a cirugía o parto

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Planned cardiac surgery with CPB
  2. Heparin-resistant patients: pre-CPB Hemochron ACT less than 480 seconds in the measurement performed between 2 and 5 minutes following intravenous administration of 500 U/kg BW UFH
  3. Patients ≥18 and ≤85 years of age
  4. Freely given written or electronic informed consent
  5. In female patients of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile), a pre-existing negative pregnancy test within 14 days prior to surgery

Exclusion criteria 9

  1. Receiving or have received one or more of the following medications within the specified time frames prior to the start of the surgery: a) vitamin K antagonists (within 3 days) b) direct oral anticoagulants (within 2 days) c) thienopyridines (ticlopidine within 14 days, prasugrel within 7 days, or clopidogrel within 5 days), unless platelet function is satisfactory d) ticagrelor (within 5 days), unless platelet function is satisfactory e) glycoprotein IIb/IIIa antagonist (within 24 hours)
  2. Pre-existing coagulopathy, a history of bleeding problems or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)
  3. Renal insufficiency, defined as serum creatinine level >2.0 mg/dL
  4. Thrombocytosis, defined as platelet count >400,000 per µL
  5. Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan and caprylic acid
  6. History of anaphylactic reaction(s) to blood or blood components
  7. Refusal to receive transfusion of blood or blood-derived products
  8. Current participation in another interventional clinical trial with an investigational medicinal product (IMP) or previous participation in the current trial
  9. Treatment with any IMP within 30 days prior to screening visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary efficacy endpoint is the percentage of patients in each group in whom no further therapy containing antithrombin (i.e., FP or other antithrombin concentrates) is needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it during CPB.

Secondary endpoints 17

  1. The comparison between the amounts of further therapy containing antithrombin (i.e., FP or antithrombin concentrates) needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it during CPB
  2. The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo
  3. The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo
  4. The comparison between heparin usage following the infusion of each of the Atenativ doses and placebo
  5. The comparison between the number of units of FP transfused for reasons other than restoring or maintaining heparin responsiveness, both intraoperatively (from the start of Atenativ or placebo infusion until the start of CPB, during CPB, and from the end of CPB until the end of surgery) and postoperatively (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first), as well as cumulatively
  6. The comparison between postoperative use of antithrombin concentrates for reasons other than restoring heparin responsiveness (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first)
  7. The comparison between transfusion of other allogeneic blood products (i.e., red blood cells [RBCs], platelets, cryoprecipitate, whole blood, albumin, other transfusion), both intraoperatively and postoperatively, as well as cumulatively
  8. The comparison between administration of coagulation factor concentrates (fibrinogen concentrate, prothrombin complex concentrate (PCC), factor XIII concentrate, recombinant activated factor VII, other therapy), both intraoperatively and postoperatively, as well as cumulatively
  9. The comparison between administration of other haemostatic-relevant therapies (i.e., tranexamic acid, aminocaproic acid, protamine, other therapies), both intraoperatively and postoperatively, as well as cumulatively
  10. The comparison between postoperative chest tube drainage volume at 24 hours after the start of Atenativ or placebo infusion, and the comparison between total chest tube drainage volume until discharge or 7 days after surgery, whichever comes first
  11. Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical)
  12. The comparison between cell saver volume until the end of surgery
  13. Incidence of AEs in the three study groups
  14. Standard haematological parameters (i.e., RBC count, white blood cell count, haemoglobin levels, haematocrit, and platelet count) following Atenativ or placebo infusion, after the end of CPB, at the end of surgery, and at 24 hours after the start of Atenativ or placebo infusion
  15. Survival status in the different treatment groups.
  16. The comparison between the amounts of further therapy containing antithrombin (i.e., FP or antithrombin concentrates) needed for restoring heparin responsiveness from the end of CPB until 24 hours after start of Atenativ or placebo infusion and from the end of CPB until discharge or 7 days postoperatively, whichever comes first
  17. Comparison of the length of ICU stay between treatment groups.

Investigational products

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

Test 12

Atenativ 50 IU/ml prášek a rozpouštědlo pro infuzní roztok

PRD310993 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
16/266/08-C
MA holder
OCTAPHARMA (IP) SPRL
MA country
Czech Republic
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ATENATIV 50 UI/mL, poudre et solvant pour solution pour perfusion

PRD7931239 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
34009 302 019 5 4
MA holder
OCTAPHARMA FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 1000 I.E. - Pulver und Lösungsmittel zur Herstellung einer Injektions- oder Infusionslösung

PRD323707 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
2-00081
MA holder
OCTAPHARMA PHARMAZEUTIKA PRODUKTIONSGESMBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 50 UI/ml pulbere și solvent pentru soluție perfuzabilă

PRD7917885 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
12981/2020/01
MA holder
OCTAPHARMA (IP) SPRL
MA country
Romania
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ, 50 IU/ml, prášek a rozpouštědlo pro infuzní roztok

PRD310992 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
16/266/08-C
MA holder
OCTAPHARMA (IP) SPRL
MA country
Czech Republic
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 50 TV/ml milteliai ir tirpiklis infuziniam tirpalui

PRD7865088 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
LT/1/20/4501/001
MA holder
OCTAPHARMA (IP) SPRL
MA country
Lithuania
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 50 TV/ml milteliai ir tirpiklis infuziniam tirpalui

PRD7865089 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
LT/1/20/4501/002
MA holder
OCTAPHARMA (IP) SPRL
MA country
Lithuania
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 50 UI/ml pulbere și solvent pentru soluție perfuzabilă

PRD7917884 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
12981/2020/02
MA holder
OCTAPHARMA (IP) SPRL
MA country
Romania
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 500 I.E. - Pulver und Lösungsmittel zur Herstellung einer Injektions- oder Infusionslösung

PRD323709 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
2-00080
MA holder
OCTAPHARMA PHARMAZEUTIKA PRODUKTIONSGESMBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 50 i.e./ml prašek in vehikel za raztopino za infundiranje

PRD7798655 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
H/19/02679/001
MA holder
OCTAPHARMA (IP) SPRL
MA country
Slovenia
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ATENATIV 50 UI/mL, poudre et solvant pour solution pour perfusion

PRD7931238 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
34009 302 019 4 7
MA holder
OCTAPHARMA FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atenativ 50 i.e./ml prašek in vehikel za raztopino za infundiranje

PRD7798656 · Product

Active substance
Antithrombin Iii Human
Substance synonyms
HUMAN ANTITHROMBIN III
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 IU/kg international unit(s)/kilogram
Max total dose
60 IU/kg international unit(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B01AB02 — ANTITHROMBIN III
Marketing authorisation
H/19/02679/002
MA holder
OCTAPHARMA (IP) SPRL
MA country
Slovenia
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Isotone Natriumchloridlösung 0,9 % Braun Injektionslösung

PRD567881 · Product

Active substance
Sodium Chloride
Substance synonyms
SODIUM CHLORID
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
1.2 millilitre(s)/kilogram
Max total dose
1.2 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
Marketing authorisation
6697366.00.00
MA holder
B.BRAUN MELSUNGEN AG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Octapharma AG

5 Total trials 4 Recruiting 1 Ended
Commercial
Sponsor organisation
Octapharma AG
Address
Seidenstrasse 2
City
Lachen Sz
Postcode
8853
Country
Switzerland

Scientific contact point

Organisation
Octapharma AG
Contact name
Sigurd Knaub

Public contact point

Organisation
Octapharma AG
Contact name
Sigurd Knaub

Third parties 7

OrganisationCity, countryDuties
Octapharma Dessau GmbH
ORG-100004022
 Dessau-Rosslau, Germany Code 14
Comac Medical Ltd.
ORG-100026829
 Sofia, Bulgaria On site monitoring, Code 12, Code 13, Code 2, Code 5
Clinigen Clinical Supplies Management GmbH
ORG-100016915
 Schwalbach Am Taunus, Germany Code 14
GBA Central Lab Services GmbH
ORG-100017343
 Schwentinental, Germany Laboratory analysis
GxP Brain GmbH
ORG-100044722
 Berlin, Germany Interactive response technologies (IRT)
Metronomia Clinical Research GmbH
ORG-100012892
 Munich, Germany Code 10, Data management, E-data capture
Optimapharm d.o.o.
ORG-100042749
 Zagreb, Croatia On site monitoring, Code 12, Code 13, Code 2, Code 5, Code 8

Locations

8 EU/EEA countries · 15 investigational sites

By country

CountryMS statusPlanned subjectsSites
Austria Ongoing, recruiting 7 2
Czechia Ongoing, recruiting 13 2
France Ended 1 2
Lithuania Ongoing, recruiting 5 2
Poland Authorised, recruitment pending 6 2
Romania Ongoing, recruiting 4 1
Slovenia Ongoing, recruiting 4 1
Spain Authorised, recruitment pending 13 3
Rest of world
United States, Serbia, United Kingdom, Canada, Kazakhstan, Turkey
 — 89 —

Investigational sites

Austria

2 sites · Ongoing, recruiting
Medical University of Vienna, AKH
Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Spitalgasse 23, A-1090, Vienna
Medizinische Universitaet Innsbruck
Department of Anaesthesia and Critical Care Medicine, Anichstrasse 35, 6020, Innsbruck

Czechia

2 sites · Ongoing, recruiting
Institute For Clinical And Experimental Medicine
Klinika anesteziologie a resuscitace, Videnska 1958/9 Krc, 140 00, Prague
Centrum kardiovaskulární a transplantační chirurgie Brno
Úsek anesteziologie, resuscitace a intenzivní medicíny, Pekařská 664/53, Czechia, Brno

France

2 sites · Ended
Centre Hospitalier Universitaire De Rennes
Cardiothoracic Intensive Care Unit, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Universitaire Reims
Anesthesie-Reanimation, Rue Du General Koenig, 51092, Reims Cedex

Lithuania

2 sites · Ongoing, recruiting
Lietuvos sveikatos mokslu universiteto ligonine Kauno klinikos
Širdies chirurgijos anesteziologijos ir intensyviosios terapijos skyriaus, Eiveniu G. 2, Kauno M. Sav., Kaunas
Vilniaus Universiteto Ligonine Santaros Klinikos Vsi
Širdies chirurgijos anesteziologijos ir intensyviosios terapijos skyriaus, Santariskiu G 2, Vilniaus M. Sav., Vilnius

Poland

2 sites · Authorised, recruitment pending
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Kliniki Anestezjologii I Intensywnej Terapii, Ul. Borowska 213, 50-556, Wroclaw
Uniwersytecki Szpital Kliniczny W Poznaniu
Oddział Kardiochirurgii i Transplantologii, Ul. Dluga 1/2, 61-848, Poznan

Romania

1 site · Ongoing, recruiting
Institutul De Urgenta Pentru Boli Cardiovasculare Prof. Dr. C. C. Iliescu
Cardiac anesthesia and intensive care medicine II, Soseaua Fundeni 258, 022328, Bucharest

Slovenia

1 site · Ongoing, recruiting
University Medical Center Ljubljana
Clinical Department of Anesthesiology and Surgical Intensive Care, Zaloska Cesta 7, 1000, Ljubljana

Spain

3 sites · Authorised, recruitment pending
Hospital Clinico San Carlos
Anesthesiology, Calle Del Profesor Martin Lagos Sn, 28040, Madrid
Hospital Universitario Y Politecnico La Fe
Anesthesiology, Avenida Fernando Abril Martorell 106, 46026, Valencia
Hospital Clinico Universitario De Valencia
Anesthesiology, Avenida Blasco Ibanez 17, 46010, Valencia

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Austria 2024-11-20 2024-11-26
Czechia 2024-12-09 2024-12-11
France 2025-01-07 2025-03-17 2025-08-08
Lithuania 2024-12-20 2025-02-05
Romania 2025-01-21 2025-01-21
Slovenia 2024-11-07 2025-02-06

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 6 · Art. 38 CTR

Temporary halt TH-94871

Halt date
2025-08-08
Member states concerned
Czechia
Publication date
2025-08-20
Reason
Sponsor decision
Explanation
The sponsor decided to pause the study to evaluate protocol design updates related to dosing. Final updates are pending IDMC review and recommendations.
The study is not put on hold due to safety reasons.
Benefit-risk balance changed
No
Treatment stopped
No

Temporary halt TH-94873

Halt date
2025-08-08
Member states concerned
France
Publication date
2025-08-20
Reason
Sponsor decision
Explanation
The sponsor decided to pause the study to evaluate protocol design updates related to dosing. Final updates are pending IDMC review and recommendations.
The study is not put on hold due to safety reasons.
Benefit-risk balance changed
No
Treatment stopped
No

Temporary halt TH-94875

Halt date
2025-08-08
Member states concerned
Lithuania
Publication date
2025-08-20
Reason
Sponsor decision
Explanation
The sponsor decided to pause the study to evaluate protocol design updates related to dosing. Final updates are pending IDMC review and recommendations.
The study is not put on hold due to safety reasons.
Benefit-risk balance changed
No
Treatment stopped
No

Temporary halt TH-94877

Halt date
2025-08-08
Member states concerned
Romania
Publication date
2025-08-20
Reason
Sponsor decision
Explanation
The sponsor decided to pause the study to evaluate protocol design updates related to dosing. Final updates are pending IDMC review and recommendations.
The study is not put on hold due to safety reasons.
Benefit-risk balance changed
No
Treatment stopped
No

Temporary halt TH-94869

Halt date
2025-08-08
Member states concerned
Austria
Publication date
2025-08-20
Reason
Sponsor decision
Explanation
The sponsor decided to pause the study to evaluate protocol design updates related to dosing. Final updates are pending IDMC review and recommendations.
The study is not put on hold due to safety reasons.
Benefit-risk balance changed
No
Treatment stopped
No

Temporary halt TH-94879

Halt date
2025-08-08
Member states concerned
Slovenia
Publication date
2025-08-20
Reason
Sponsor decision
Explanation
The sponsor decided to pause the study to evaluate protocol design updates related to dosing. Final updates are pending IDMC review and recommendations.
The study is not put on hold due to safety reasons.
Benefit-risk balance changed
No
Treatment stopped
No

Results and documents

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

Documents 42 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol amendment_2023-507560-39_redacted 07
Protocol (for publication) D1_Protocol_2023-507560-39_redacted 09
Recruitment arrangements (for publication) K1_Recruitment and informed consent procedure NA
Recruitment arrangements (for publication) K1_Recruitment and informed consent procedure NA
Recruitment arrangements (for publication) K1_Recruitment and informed consent procedure NA
Recruitment arrangements (for publication) K1_Recruitment arrangements NA
Recruitment arrangements (for publication) K1_Recruitment arrangements N/A
Recruitment arrangements (for publication) K1_Recruitment arrangements_FR_unredacted NA
Recruitment arrangements (for publication) K1_Recruitment Arrangements_PL 2.0
Recruitment arrangements (for publication) K1_Recruitment arrangements_Public NA
Subject information and informed consent form (for publication) L1_SIS and ICF 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Main_PL 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF Main_Public 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF Secondary Use Data_Public 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Contact details NA
Subject information and informed consent form (for publication) L1_SIS and ICF_GDPR_unredacted 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Main 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Main_FR_unredacted 5.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Main_unredacted 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Main_unredacted 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Main_unredacted 5.0
Subject information and informed consent form (for publication) L2_ATN-108_Patient Card_Public 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_patient card 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_CZ NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_DE AT NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_EN NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_FR NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_LT NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_RO NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Atenativ_SI NA
Synopsis of the protocol (for publication) D1_Protocol synopsis full_DE_2023-507560-39_06 06
Synopsis of the protocol (for publication) D1_Protocol synopsis full_DE_2023-507560-39_09 09
Synopsis of the protocol (for publication) D1_Protocol synopsis full_LT_2023-507560-39 06
Synopsis of the protocol (for publication) D1_Protocol synopsis_CZ_2023-507560-39 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_DE AT_2023-507560-39 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_EN_2023-507560-39 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_ES_2023-507560-39 09
Synopsis of the protocol (for publication) D1_Protocol synopsis_FR_2023-507560-39 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_full LT_2023-507560-39 09
Synopsis of the protocol (for publication) D1_Protocol synopsis_LT_2023-507560-39 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_RO_2023-507560-39 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_SI_2023-507560-39 2.0

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-04-15 Czechia Acceptable with conditions
2024-08-01
 2024-08-01
2 SUBSTANTIAL MODIFICATION SM-1 2024-08-29 Acceptable with conditions 2024-09-20
3 SUBSTANTIAL MODIFICATION SM-2 2024-10-29 Czechia Acceptable
2025-02-13
 2025-02-14
4 NON SUBSTANTIAL MODIFICATION NSM-1 2025-02-21 Czechia Acceptable
2025-02-13
 2025-02-21
5 NON SUBSTANTIAL MODIFICATION NSM-2 2025-04-03 Czechia Acceptable
2025-02-13
 2025-04-03
6 SUBSTANTIAL MODIFICATION SM-3 2025-04-11 Czechia Acceptable with conditions
2025-07-21
 2025-07-21
7 NON SUBSTANTIAL MODIFICATION NSM-3 2025-08-01 Acceptable with conditions
2025-07-21
 2025-08-01
8 SUBSTANTIAL MODIFICATION SM-4 2025-09-30 Czechia Acceptable
2025-12-17
 2025-12-17
9 SUBSEQUENT ADDITION OF MSC APP-9 2026-01-15 Acceptable
2025-12-17
 2026-04-09
10 SUBSEQUENT ADDITION OF MSC APP-10 2026-01-21 2026-03-27
11 NON SUBSTANTIAL MODIFICATION NSM-4 2026-04-13 Czechia 2026-04-13