A contrast medium sparing strategy using automated Carbon Dioxide Injection during PERIpheral vascular interventions for PREVENTion of Major Adverse Kidney Events (MAKE): the PeriPREVENT randomized controlled trial

2024-512876-37-00 Protocol PeriPREVENT Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 11 Apr 2025 · Status Ongoing, recruiting · 2 EU/EEA countries · 14 sites · Protocol PeriPREVENT

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 1,960
Countries 2
Sites 14

Peripheral Arterial Disease (PAD)

The primary objective of the trial is to evaluate if an iodinated contrast medium sparing strategy using automated Carbon Dioxide (CO2) Injection prevents Major Adverse Kidney Events up to 90 days (MAKE90) in patients at moderately elevated risk for contrast-associated acute kidney injury (CA-AKI) undergoing infraingui…

Key facts

Sponsor
Universitaet Leipzig
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
11 Apr 2025 → ongoing
Decision date (initial)
2024-10-29
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No
Funding sources
German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the trial is to evaluate if an iodinated contrast medium sparing strategy using automated Carbon Dioxide (CO2) Injection prevents Major Adverse Kidney Events up to 90 days (MAKE90) in patients at moderately elevated risk for contrast-associated acute kidney injury (CA-AKI) undergoing infrainguinal peripheral vascular interventions (PVI).

Secondary objectives 2

  1. Main secondary objective is to evaluate if an iodinated contrast medium sparing strategy using automated Carbon Dioxide (CO2) Injection prevents post-procedural acute kidney injury (AKI).
  2. In addition, the iodinated contrast medium sparing strategy will be compared to the standard of care strategy with iodinated contrast medium with respect to: • Other indicators for kidney injury, such as Major Adverse Kidney Events at discharge and single components of MAKE90 • Technical as well as procedural success • Intra-procedural, in-hospital and 90 days safety • 1-year mortality.

Conditions and MedDRA coding

Peripheral Arterial Disease (PAD)

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Treatment Period
Patients undergo peripheral vascular intervention with either iodinated contrast medium or CO2.
 Randomised Controlled None control: iodinated contrast medium
intervention: CO2
2 Follow-up Period
After the peripheral vascular intervention all patients are followed up one year.
 Not Applicable None all patients: all patients are followed up equally

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Symptomatic peripheral arterial disease presenting with either acute symptoms (Rutherford clinical categories I-IIb) or chronic symptoms (Fontaine stages IIb-IV or Rutherford clinical categories 2-6)
  2. Planned peripheral vascular intervention of infrainguinal arteries due to femoropopliteal and/or infrapopliteal lesions
  3. Increased risk of CA-AKI identified by a baseline risk score of ≥ 5 points based on a published dedicated PVI risk score [1] and a pre-angiographic estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m²
  4. Both angiographic strategies seem feasible at the investigator’s discretion
  5. Age 18 years or older
  6. Written informed consent

Exclusion criteria 19

  1. Very agitated patients
  2. Patients with planned full anaesthesia during procedure
  3. Patients with a life-expectancy less than one year
  4. Patients confined to bed that are completely non-ambulatory
  5. Known acute renal failure or known unstable renal function as evidenced by a recent increase in serum creatinine (SCr) of > 0.5 mg/dl or > 25% within 7 days
  6. Iodinated contrast medium exposure within 7 days prior to procedure with change in SCr ≥ 0.1 mg/dl on two SCr measures ≥ 24 h apart
  7. Advanced chronic kidney disease (CKD) with an eGFR < 20 ml/min/1.73 m² and/or dialysis
  8. Current use of nephrotoxic agents (aminoglycoside antibiotics, sulfonamides, amphotericin B, or pentamidine), or an active chemotherapy agent
  9. Acute or chronic pulmonary disease requiring oxygen therapy
  10. Patients with known patent foramen ovale or atrial septal defect
  11. Patients with planned nitrous oxide anaesthesia during intervention
  12. Patients with manifest hyperthyroidism or manifest thyrotoxicosis
  13. Known allergies or hypersensitivity to iodinated contrast media that cannot be adequately pre-treated prior to index procedure
  14. Planned further procedure with a need for > 10 ml of iodinated contrast medium (CM) in any location (e.g., CT scan, coronary angiography) within a period of 90 days
  15. Any surgical procedure (except minor amputations) or intervention performed within 30 days prior to or planned within 90 days post index procedure
  16. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) until day 30 after PVI.
  17. Previous participation in the PeriPREVENT trial or participation in other interventional trials. (Exceptions are described in the trial protocol)
  18. Suspected lack of compliance
  19. Pregnant or nursing women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Major Adverse Kidney Events up to day 90 after intervention (MAKE90)

Secondary endpoints 6

  1. Main Secondary Endpoint: Post-procedural acute kidney injury (AKI)
  2. Major Adverse Kidney Events (MAKE) endpoint up to day 7 (MAKE-7)
  3. Single components of MAKE90
  4. Major Adverse Kidney Events at 90 days considering a drop in eGFR by at least 40% (instead of 25% as for the primary endpoint) as compared to baseline
  5. Technical success
  6. Procedural success

Investigational products

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

Test 17

VISIPAQUETM 320 mg/ml Injektionslösung

PRD315606 · Product

Active substance
Iodixanol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
6.25 millilitre(s)/kilogram
Max total dose
6.25 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB09 — IODIXANOL
Marketing authorisation
32292.02.00
MA holder
GE HEALTHCARE BUCHLER GMBH & CO. KG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

VISIPAQUETM 270 mg/ml Injektionslösung

PRD315603 · Product

Active substance
Iodixanol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
7.41 millilitre(s)/kilogram
Max total dose
7.41 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB09 — IODIXANOL
Marketing authorisation
32292.01.00
MA holder
GE HEALTHCARE BUCHLER GMBH & CO. KG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Solutrast 200, 200 mg Iod/ml, Injektionslösung

PRD465937 · Product

Active substance
Iopamidol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
7.5 millilitre(s)/kilogram
Max total dose
7.5 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB04 — IOPAMIDOL
Marketing authorisation
29273.00.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Solutrast 300, 300 mg Iod/ml, Injektionslösung

PRD465938 · Product

Active substance
Iopamidol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
5 millilitre(s)/kilogram
Max total dose
5 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB04 — IOPAMIDOL
Marketing authorisation
29273.01.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Solutrast 250, 250 mg Iod/ml, Injektionslösung

PRD465964 · Product

Active substance
Iopamidol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
6 millilitre(s)/kilogram
Max total dose
6 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB04 — IOPAMIDOL
Marketing authorisation
4378.03.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Solutrast 370, 370 mg Iod/ml, Injektionslösung

PRD465963 · Product

Active substance
Iopamidol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
4.1 millilitre(s)/kilogram
Max total dose
4.1 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB04 — IOPAMIDOL
Marketing authorisation
4378.02.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Optiray 320 mg Iod/ml Injektionslösung/Infusionslösung

PRD4083997 · Product

Active substance
Ioversol
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
250 ml millilitre(s)
Max total dose
250 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB07 — IOVERSOL
Marketing authorisation
16284.03.00
MA holder
GUERBET
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ACCUPAQUE™ 350 Injektionslösung oder Lösung zum Einnehmen

PRD1804684 · Product

Active substance
Iohexol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
4.3 millilitre(s)/kilogram
Max total dose
4.3 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB02 — IOHEXOL
Marketing authorisation
3004003.00.00
MA holder
GE HEALTHCARE BUCHLER GMBH & CO. KG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ACCUPAQUE™ 300 Injektionslösung oder Lösung zum Einnehmen

PRD1804460 · Product

Active substance
Iohexol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
5 millilitre(s)/kilogram
Max total dose
5 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB02 — IOHEXOL
Marketing authorisation
3004002.00.00
MA holder
GE HEALTHCARE BUCHLER GMBH & CO. KG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ACCUPAQUE™ 240 Injektionslösung

PRD318523 · Product

Active substance
Iohexol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
6.25 millilitre(s)/kilogram
Max total dose
6.25 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB02 — IOHEXOL
Marketing authorisation
3004004.00.00
MA holder
GE HEALTHCARE BUCHLER GMBH & CO. KG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Imeron 300, 300 mg Iod/ml, Injektionslösung, Infusionslösung

PRD464312 · Product

Active substance
Iomeprol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
250 ml millilitre(s)
Max total dose
250 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB10 — IOMEPROL
Marketing authorisation
30699.03.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Imeron 400, 400 mg Iod/ml, Injektionslösung, Infusionslösung

PRD464314 · Product

Active substance
Iomeprol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
250 ml millilitre(s)
Max total dose
250 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB10 — IOMEPROL
Marketing authorisation
30699.05.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Imeron 350, 350 mg Iod/ml, Injektionslösung, Infusionslösung

PRD464313 · Product

Active substance
Iomeprol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
250 ml millilitre(s)
Max total dose
250 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB10 — IOMEPROL
Marketing authorisation
30699.04.00
MA holder
BRACCO IMAGING DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Jopamiro 370 mg J/ml - Stechampullen

PRD465931 · Product

Active substance
Iopamidol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
50 ml millilitre(s)
Max total dose
50 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB04 — IOPAMIDOL
Marketing authorisation
17.304
MA holder
BRACCO ÖSTERREICH GMBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ultravist®-240, 240 mg Iod/ml, Injektions- oder Infusionslösung

PRD388852 · Product

Active substance
Iopromide
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
6.25 millilitre(s)/kilogram
Max total dose
6.25 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB05 — IOPROMIDE
Marketing authorisation
5642.00.00
MA holder
BAYER VITAL GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ultravist®-370, 370 mg Iod/ml, Injektions- oder Infusionslösung oder Lösung zum Einnehmen

PRD388853 · Product

Active substance
Iopromide
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
4 millilitre(s)/kilogram
Max total dose
4 millilitre(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB05 — IOPROMIDE
Marketing authorisation
5642.02.00
MA holder
BAYER VITAL GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ultravist®-300, 300 mg Iod/ml, Injektions- oder Infusionslösung oder Lösung zum Einnehmen

PRD393660 · Product

Active substance
Iopromide
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INJECTION, IV INFUSION
Max daily dose
150 ml millilitre(s)
Max total dose
150 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB05 — IOPROMIDE
Marketing authorisation
5642.01.00
MA holder
BAYER VITAL GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Leipzig

5 Total trials 3 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Universitaet Leipzig
Address
Ritterstrasse 26, Zentrum Zentrum
City
Leipzig
Postcode
04109
Country
Germany

Scientific contact point

Organisation
Universitaet Leipzig
Contact name
Prof. Dr. Sabine Steiner

Public contact point

Organisation
Universitaet Leipzig
Contact name
Prof. Dr. Sabine Steiner

Locations

2 EU/EEA countries · 14 investigational sites

By country

CountryMS statusPlanned subjectsSites
Austria Ongoing, recruiting 392 2
Germany Ongoing, recruiting 1,568 12
Rest of world — 0 —

Investigational sites

Austria

2 sites · Ongoing, recruiting
Medizinische Universitaet Innsbruck
Department of Radiology, Anichstrasse 35, 6020, Innsbruck
Medical University Of Vienna
Department of Angiology, Waehringer Guertel 18-20, Alsergrund, Vienna

Germany

12 sites · Ongoing, recruiting
University Medical Center Hamburg-Eppendorf
Klinik für Herz- und Gefäßmedizin, Martinistrasse 52, Eppendorf, Hamburg
Universitaetsklinikum Leipzig AöR
Klinik und Poliklinik für Angiologie, Liebigstrasse 20, Zentrum-Suedost, Leipzig
SANA Kliniken Oberfranken Coburg GmbH
Klinik für Gefäßmedizin, Ketschendorfer Strasse 33, 96450, Coburg
Medical Center - University Of Freiburg
Klinik für Kardiologie und Angiologie, Suedring 15, 79189, Bad Krozingen
DIAKO Krankenhaus gGmbH
Diagnostische und Interventionelle Radiologie Neuroradiologie, Knuthstrasse 1, Neustadt, Flensburg
Klinikum rechts der Isar der TU Muenchen AöR
Klinik und Poliklinik für Vaskuläre und Endovaskuläre Chirurgie, Ismaninger Strasse 22, Au-Haidhausen, Munich
Klinikum Chemnitz gGmbH
Klinik für Thorax- und Gefäßchirurgie, Flemmingstrasse 4, Altendorf, Chemnitz
MVZ CCB Frankfurt Und Main-Taunus GbR
Gefaess Centrum, Im Pruefling 23, Bornheim, Frankfurt Am Main
Kreiskrankenhaus des Vogelsbergkreises in Alsfeld GmbH
Gefäßchirurgie, Schwabenröder Straße 81, 36304, Alsfeld
Universitaetsklinikum Bonn AöR
Klinik für Angiologie, Venusberg-Campus 1, Venusberg, Bonn
Evangelisches Krankenhaus Konigin Elisabeth Herzberge gGmbH
Gefäßzentrum, Herzbergstrasse 79, Lichtenberg, Berlin
GRN Gesundheitszentren Rhein-Neckar gGmbH
Abteilung Innere Meidzin: Kardiologie und Angiologie, Roentgenstrasse 1, 69469, Weinheim

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 2025-04-11 2025-04-14
Germany 2025-08-13 2025-08-15

Results and documents

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

Documents 20 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-512876-37-00_p 4
Protocol (for publication) D1_Protocol_2024-512876-37-00_TC_p 1
Recruitment arrangements (for publication) K1_Recruitment_arrangements 1
Recruitment arrangements (for publication) K1_Recruitment_arrangements 1
Subject information and informed consent form (for publication) L1_Centre_specific_contact_list_ICF_p 1
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Austria 1
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Austria_TC 1
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Biobanking 1
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Biobanking_TC 1
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Germany 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Accupaque_Iohexol_2022-07 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Imeron_Iomeprol_2022-04 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Jopamiro370_Iopamidol_2022-10 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Optiray_Ioversol_2022-09 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Solutrast_Iopamidol_2022-10 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Ultravist_Iopromid_2025-02 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Visipaque_Iodixanol_2022-04 2
Synopsis of the protocol (for publication) D1_Protocol_synopsis_DE_2024-512876-37-00 4
Synopsis of the protocol (for publication) D1_Protocol_synopsis_DE_2024-512876-37-00_TC 4
Synopsis of the protocol (for publication) D1_Protocol_synopsis_ENG_2024-512876-37-00_TC 4

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-10 Germany Acceptable
2024-10-24
 2024-10-25
2 SUBSTANTIAL MODIFICATION SM-1 2025-09-08 Germany Acceptable
2025-10-29
 2025-10-29
3 SUBSTANTIAL MODIFICATION SM-2 2026-04-02 Germany Acceptable
2026-05-19
 2026-05-21

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