A prospective randomized, single-blind, multicenter phase II study comparing two methods of cardioplegia in cardiac surgery due to congenital heart malformation in children: Custodiol-N versus Custodiol (CL-N-CP-Paed-II/09/19)

2024-511517-38-00 Protocol CL-N-CP-Paed Therapeutic exploratory (Phase II) Temporarily halted

Start 5 Nov 2024 · Status Temporarily halted · 1 EU/EEA countries · 3 sites · Protocol CL-N-CP-Paed

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Temporarily halted
Participants planned 100
Countries 1
Sites 3

congenital heart malformation inchildren

The main purpose of the clinical trial is safety assessment regarding • Continuous adverse events (AEs) reporting up to 30 days postoperatively • Myocardial protection in surviving patients, as assessed by quantification of perioperative CK-MB levels (U/l) until postoperative day 2 and postoperative day 7 or discharge

Key facts

Sponsor
Dr. Franz Koehler Chemie GmbH
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
5 Nov 2024 → ongoing
Decision date (initial)
2024-08-16
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

The main purpose of the clinical trial is safety assessment regarding
• Continuous adverse events (AEs) reporting up to 30 days postoperatively
• Myocardial protection in surviving patients, as assessed by quantification of perioperative CK-MB levels (U/l) until postoperative day 2 and postoperative day 7 or discharge

Secondary objectives 7

  1. Description of hemodynamics (incl. vitals signs, blood gas parameters, catecholamine support, milrinone support)
  2. Description of echo
  3. Description of cardiac injury (incl. creatinine kinase, troponin)
  4. Hospital/ ICU stay (readmissions, duration)/ Death
  5. Description of surgery (incl. number of intraoperative administrations/re-administrations of cardioplegia)
  6. Description of 12-Lead-ECG
  7. Description of cardiac arrhythmias (incl. need for pacemaker)

Conditions and MedDRA coding

congenital heart malformation inchildren

Regulatory references

EMA paediatric investigation plan (PIP)
EMEA-002735-PIP01-19
Plan to share IPD
No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Age from birth to less than 18 years of age
  2. congenital heart surgery with cardiopulmonary bypass and cardioplegia
  3. written informed consent of the patients and/ or their legal guardians (must be available before enrolment in the study)
  4. Ability of the legal guardians to understand character and individual consequences of the clinical trial

Exclusion criteria 4

  1. Patients who have participated within 30 days or are still participating in any other interventional study
  2. History of severe organic (e.g. liver or kidney) disease other than concerning the heart
  3. History of psychiatric disease
  4. Pregnancy and lactation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The main purpose of the clinical trial is safety assessment regarding • Continuous adverse events (AEs) reporting up to 30 days postoperatively • Myocardial protection in surviving patients, as assessed by quantification of perioperative CK-MB levels (U/l) until day 7 postoperatively (Area under the curve)

Secondary endpoints 7

  1. Description of hemodynamics (incl. vitals signs, blood gas parameters, catecholamine support, milrinone support)
  2. Description of echo
  3. Description of cardiac injury (incl. creatinine kinase, troponin)
  4. Hospital/ ICU stay (readmissions, duration)/ Death
  5. Description of surgery (incl. number of intraoperative administrations of cardioplegia)
  6. Description of 12-Lead-ECG
  7. Description of cardiac arrhythmias (incl. need for pacemaker)

Investigational products

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

Test 1

Custodiol-N

PRD11169162 · Product

Active substance
Alanine
Pharmaceutical form
SOLUTION FOR ORGAN PRESERVATION
Route of administration
INFILTRATION
Max daily dose
60 millilitre(s)/kilogram
Max total dose
60 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
DR. FRANZ KÖHLER CHEMIE GMBH
Paediatric formulation
No
Orphan designation
No

Comparator 1

CUSTODIOL® - Perfusionslösung

PRD2221806 · Product

Active substance
Mannitol
Pharmaceutical form
SOLUTION FOR CARDIOPLEGIA
Route of administration
INFILTRATION
Max daily dose
50 millilitre(s)/kilogram
Max total dose
50 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B05XA16 — CARDIOPLEGIA SOLUTIONS
Marketing authorisation
1-20642
MA holder
DR. FRANZ KÖHLER CHEMIE GMBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dr. Franz Koehler Chemie GmbH

4 Total trials 2 Recruiting 1 Ended
Commercial
Sponsor organisation
Dr. Franz Koehler Chemie GmbH
Address
Werner-Von-Siemens-Strasse 14- 28
City
Bensheim
Postcode
64625
Country
Germany

Scientific contact point

Organisation
Dr. Franz Koehler Chemie GmbH
Contact name
PD Dr. Philippe Grieshaber

Public contact point

Organisation
Dr. Franz Koehler Chemie GmbH
Contact name
PD Dr. Philippe Grieshaber

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Temporarily halted 100 3
Rest of world — 0 —

Investigational sites

Germany

3 sites · Temporarily halted
Universitaetsklinikum Giessen und Marburg GmbH
Kinderherzzentrum, Klinikum für Kinderherzchirurgie, Feulgenstrasse 10-12, 35392, Giessen
Deutsches Herzzentrum Muenchen Des Freistaates Bayern Klinik An Der Technischen Universitaet Muenchen
Deutsches Herzzentum München, Lazarettstrasse 36, Neuhausen-Nymphenburg, Munich
Universitaetsklinikum Muenster AöR
Klinik für Herz- und Thoraxchirurgie, Albert-Schweitzer-Campus 1, Sentrup, Muenster

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Germany 2024-11-05 2025-08-28 2025-09-30

Oversight and notifications

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

Temporary halts 1 · Art. 38 CTR

Temporary halt TH-99873

Halt date
2025-09-30
Planned restart
2027-09-29
Member states concerned
Germany
Publication date
2025-09-30
Reason
Sponsor decision
Explanation
The sponsor is temporarily suspending the study for purely financial and not because of safety reasons. All trial sites have already been informed, and no further patients can be enrolled in the study because no study medication is currently available at the sites. The enrolled patient has completed the study and no further activities are necessary.
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 15 files

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

TypeTitleVersion
Protocol (for publication) D1_Custodiol_N_CP_Paed_Protocol_public 2
Protocol (for publication) Placeholder_revised CTIS transparency rules 1
Protocol (for publication) Placeholder_revised CTIS transparency rules_1 1
Recruitment arrangements (for publication) K1_list_German_trial_sites_Number_of_participants 1
Recruitment arrangements (for publication) K1_Recruitment arrangement 1
Subject information and informed consent form (for publication) L1_Custodiol_N_CP_Paed_IC_parent 4
Subject information and informed consent form (for publication) L1_Custodiol_N_CP_Paed_IC_parent_TC 1
Subject information and informed consent form (for publication) L1_Custodiol_N_CP-Paed_IC_Age_12-17 2
Subject information and informed consent form (for publication) L1_Custodiol_N_CP-Paed_IC_Age_7-11 3
Subject information and informed consent form (for publication) L1_Custodiol_N_CP-Paed_IC_Age_7-11_TC 1
Subject information and informed consent form (for publication) Placeholder_revised CTIS transparency rules_2 1
Summary of Product Characteristics (SmPC) (for publication) G1_CL-N-CP-Paed_SmPC_Custodiol 1
Summary of Product Characteristics (SmPC) (for publication) Placeholder IB 1
Synopsis of the protocol (for publication) D1_Custodiol_N_CP_Paed_Protocol_Synopis 2
Synopsis of the protocol (for publication) Placeholder_revised CTIS transparency rules 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-05-15 Germany Acceptable
2024-07-29
 2024-08-16
2 NON SUBSTANTIAL MODIFICATION NSM-1 2024-08-22 Germany Acceptable
2024-07-29
 2024-08-22
3 SUBSTANTIAL MODIFICATION SM-1 2025-02-27 Germany Acceptable
2025-03-20
 2025-03-28

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