Antioxidant Treatment with Vitamin C in Cardiac Surgery Patients - A Pilot Randomized Controlled Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GCP-Service International West GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

19 Jul 2024 → ongoing

Decision date (initial)

2024-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pascoe pharmazeutische Präparate GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy

The primary objective is to assess efficacy of vitamin C compared to standard of care in reducing the systemic inflammatory reaction from before cardiac surgery until 72 hours after surgery.

Secondary objectives 5

1. Further evaluate efficacy of the investigational medicinal product by its effects on clinically relevant outcomes such as organ dysfunction, the duration of mechanical ventilation, intensive care unit (ICU) and hospital length of stay and mortality rates.
2. Collect information on safety parameters including all AEs, SAEs, IMP related AEs, AEs leading to study discontinuation and AESIs.
3. Exploratory objective: Explore the feasibility of the study including recruitment rate and compliance rate.
4. Exploratory objective: Evaluate whether a clear distinction can be made between the intervention- and control-group regarding the vitamin C serum levels and intracellular vitamin C.
5. Exploratory objective: Collect further information on efficacy and safety parameters

Conditions and MedDRA coding

Cardiovascular illness, Intensive care unit (ICU), open-heart surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Written informed consent prior to study participation
2. Adult patients (≥ 18 years)
3. Patients undergoing open-heart surgery with the use of cardiopulmonary bypass (CPB), who are defined as high risk based on having (i) combined valve or CABG or multiple valve surgeries, or combined cardiac/aortic surgical procedures and (ii) at least one of the following additional risk factors: a. a high perioperative risk profile, defined as a predicted operative mortality of ≥ 8% (EuroSCORE II) b. Age >70 years c. Clinical Frailty Scale >4 d. Urgent need for cardiac surgery (defined as to be performed within 24 to 48 hours after admission to hospital). e. Left ventricular ejection fraction <35%
4. The investigator considers the patient to be suitable for participating in the study

Exclusion criteria 10

1. Patients with history of recurrent formation of kidney stones (oxalate urolithiasis) or recent history (within 1 year) of any kidney stones
2. Patients with severe renal insufficiency (CKD KDIGO Stage 4/5 or glomerular filtration rate < 30 ml/min)
3. Patients with known glucose-6-phosphate dehydrogenase deficiency.
4. Patients with known thalassemia, hemochromatosis and sideroblastic anemia.
5. Patients with known hypersensitivity to the Investigational Medicinal Product (IMP) or against any of its ingredients
6. Patients who are pregnant or lactating
7. Patients who are receiving high-dose IV vitamin C (enteral or oral vitamin C is allowed) already before surgery (>100 mg/kg/day as daily dose for > 1 week
8. Patients who are moribund (not expected to survive the next 72 hours from screening evaluation)
9. Patients with severe acid-base or electrolyte imbalances
10. Patients who are enrolled in industry sponsored interventional trials. The enrolment of patients included in interventional investigator-initiated trials will be discussed on a case-by-case depending on potential confounders regarding this trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The area under the curve of serum levels of IL-6 from baseline to 72 hours after surgery

Secondary endpoints 22

1. 30 day and 6-month all-cause mortality
2. Days alive and out of hospital
3. Time to discharge alive (TDA)
4. Persistent organ dysfunction and death
5. ICU and hospital length of stay
6. ICU and hospital readmission rates
7. Area under the curve (AUC) of inflammatory markers (IL-1b, TNF-α and IFN-γ)
8. Absolute values of daily measurements of C Reactive Protein (CRP), procalcitonin (PCT) and leukocytes during ICU stay
9. Daily overall Sequential Organ Failure Assessment (SOFA) Score
10. Duration and type (invasive or non-invasive) of mechanical ventilation
11. Duration and dosage of sedative agents used postoperatively
12. Occurrence of malignant arrhythmias
13. Occurrence of atrial fibrillation
14. Left ventricular ejection fraction (LVEF)
15. New York Heart Association (NYHA) Classification
16. Number of cerebral ischemic or hemorrhagic events
17. Clinical Frailty Scale (CFS)
18. Daily Confusion Assessment Method for the ICU (CAM-ICU) Score
19. Urine output during the ICU length of stay
20. Number of post operative complications including surgical re-evaluation, severe hemorrhage requiring surgical intervention, thromboembolic events requiring intervention, infection and sepsis
21. Adverse Events leading to discontinuation/Adverse Events at least possibly related to the IMP/Serious Adverse Events and Adverse Events of Special Interest
22. Entzündungsmarker, die mit Point-of-Care-Methoden am Krankenbett analysiert werden (z. B. IL-1, IL-6, IL-8, IL-10, TNF-α, IFN-γ, CRP, PCT, D-Dimer, Ferritin)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GCP-Service International West GmbH

Sponsor organisation

GCP-Service International West GmbH

Address

Siegfeldstrasse 11

City

Siegburg

Postcode

53721

Country

Germany

Scientific contact point

Organisation

GCP-Service International West GmbH

Contact name

sponsor representative

Public contact point

Organisation

GCP-Service International West GmbH

Contact name

sponsor representative

Third parties 3

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 5 files

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

Application history

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