Intraperitoneal treatment with fosfomycin, metronidazole and recombinant human granulocyte-macrophage colony-stimulating factor in patients with multi-quadrant peritonitis undergoing abdominal surgery: A randomized placebo-controlled trial (TRIPLE)

2024-520317-49-02 Protocol 2025-GMF-1 Human pharmacology (Phase I) - Other Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 2 sites · Protocol 2025-GMF-1

Overview

Sponsor-declared trial summary

Phase Human pharmacology (Phase I) - Other
Status Authorised, recruitment pending
Participants planned 32
Countries 1
Sites 2

peritonitis

To investigate if intraperitoneal administration of GM-CSF, metronidazole and fosfomycin can optimize the treatment of patients with multiquadrant peritonitis

Key facts

Sponsor
Region Sjaelland, Reponex Pharmaceuticals A/S
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Digestive System Diseases [C06]
Decision date (initial)
2025-08-22
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy

To investigate if intraperitoneal administration of GM-CSF, metronidazole and fosfomycin can optimize the treatment of patients with multiquadrant peritonitis

Conditions and MedDRA coding

peritonitis

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 TRIPLE
To investigate if intraperitoneal administration of GM-CSF, metronidazole and fosfomycin can optimize the treatment of patients with multiquadrant peritonitis
 Randomised Controlled None Arm A: Intervention (GM-CSF + Metronidazole + Fosfomycin)
Arm B: Placebo (Saline)

Regulatory references

Plan to share IPD
Yes
EU CT numberTitleSponsor
2024-520317-49-00 Intraperitoneal treatment with fosfomycin, metronidazole and recombinant human granulocyte-macrophage colony-stimulating factor in patients with multi-quadrant peritonitis undergoing abdominal surgery: A randomized placebo-controlled trial (TRIPLE) Region Sjaelland
2024-520317-49-01 Intraperitoneal treatment with fosfomycin, metronidazole and recombinant human granulocyte-macrophage colony-stimulating factor in patients with multi-quadrant peritonitis undergoing abdominal surgery: A randomized placebo-controlled trial (TRIPLE) Region Sjaelland

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. - All patients age ≥ 18 undergoing surgical intervention with findings of peritonitis, due to a lesion in the large intestine, with the involvement of ≥2 quadrants

Exclusion criteria 1

  1. - Patients with a previous allergic reaction to rhGM-CSF, fosfomycin or metronidazole - Patients with American Society of Anesthesiologists (ASA) physical status >3 - Patients with WHO Performance status >3 - Patients with peritoneal carcinomatosis - Patients currently in treatment for any malignant or hematological disease - Patients active prescribed immunosuppressants - Patients with an autoimmune disease in active treatment with immunomodulatory drugs - Patients with the need of vacuum assisted closure (VAC) - Participating in another pharmacological intervention trial - Patients currently pregnant or breastfeeding. - Patients with severe renal failure (eGFR < 30 ml/min) - Patients with anticipated compliance problems as determined by the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Clinical failure at POD28 (composite outcome: either death, surgical site wound infection, unplanned surgery or drainage due to complication or recurrence of intraabdominal infection or initiation of non-trial antibiotics due to worsening of intraabdominal infection)

Secondary endpoints 8

  1. Macrophage phagocytosis assay on PBMCs
  2. Change in cytokine levels in peripheral blood
  3. Change in various blood values: • Hematology, • K+, • Na+, • CRP, • Albumin, • Creatinine (incl. eGFR)
  4. Quality of recovery-15
  5. Postoperative complications according to Clavien-Dindo
  6. Length of hospital stay
  7. length of intensive care unit stay
  8. Duration of intravenous antibiotics treatment

Investigational products

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

Test 3

Fosfomycin "Infectopharm", pulver til infusionsvæske, opløsning 40 mg/ml

PRD12029247 · Product

Active substance
Fosfomycin
Substance synonyms
(3-METHYLOXIRAN-2-YL)PHOSPHONIC ACID, PHOSPHOMYCIN, PHOSPHONOMYCIN
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRA-ABDOMINAL USE
Max daily dose
4 g gram(s)
Max total dose
4 g gram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J01XX01 — FOSFOMYCIN
Marketing authorisation
58248
MA holder
INFECTOPHARM ARZNEIMITTEL UND CONSILIUM GMBH, DE, HEPPENHEIM
MA country
Denmark
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Repomol

PRD12771887 · Product

Active substance
Molgramostim
Substance synonyms
SCH-39300
Pharmaceutical form
INTRAPERITONEAL SOLUTION
Route of administration
INTRA-ABDOMINAL USE
Max daily dose
50 µg microgram(s)
Max total dose
50 µg microgram(s)
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
REGION HOVEDSTADENS APOTEK
Paediatric formulation
No
Orphan designation
No

Metronidazol ”Baxter” Viaflo, infusionsvæske, opløsning

PRD12010530 · Product

Active substance
Metronidazole
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRA-ABDOMINAL USE
Max daily dose
500 mg milligram(s)
Max total dose
500 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
P01AB01, J01XD01 — METRONIDAZOLE, METRONIDAZOLE
Marketing authorisation
34620
MA holder
BAXTER A/S
MA country
Denmark
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Saline Solution Basi 9 mg/ml solution for infusion

PRD11121726 · Product

Active substance
Sodium Chloride
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRA-ABDOMINAL USE
Max daily dose
500 ml millilitre(s)
Max total dose
500 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B05XA03 — SODIUM CHLORIDE
Marketing authorisation
5211800
MA holder
LABORATÓRIOS BASI – INDÚSTRIA FARMACÊUTICA, S.A.
MA country
Malta
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Sjaelland

14 Total trials 7 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Region Sjaelland
Address
Lykkebaekvej 1
City
Koege
Postcode
4600
Country
Denmark

Scientific contact point

Organisation
Region Sjaelland
Contact name
Ismail Gögenur

Public contact point

Organisation
Region Sjaelland
Contact name
Ismail Gögenur

Third parties 1

OrganisationCity, countryDuties
Frederiksberg Hospital
ORG-100028217
 Frederiksberg, Denmark On site monitoring

Reponex Pharmaceuticals A/S

3 Total trials 1 Recruiting
Commercial
Sponsor organisation
Reponex Pharmaceuticals A/S
Address
Slotsmarken 12, 1 Th
City
Hoersholm
Postcode
2970
Country
Denmark

Scientific contact point

Organisation
Region Sjaelland
Contact name
Ismail Gögenur

Public contact point

Organisation
Region Sjaelland
Contact name
Ismail Gögenur

Sponsor responsibilities

Article 77 compliance
Region Sjaelland
Contact point sponsor
Region Sjaelland
Article 77 implementation
Region Sjaelland

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Authorised, recruitment pending 32 2
Rest of world — 0 —

Investigational sites

Denmark

2 sites · Authorised, recruitment pending
Slagelse Hospital
Department of Surgery, Slagelse Hospital, Ingemannsvej 18, 4200, Slagelse
Region Sjaelland
Center for Surgical Science, Department of Surgery, Lykkebaekvej 1, 4600, Koege

Results and documents

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

Documents 7 files

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

TypeTitleVersion
Protocol (for publication) peritonitis protocol clean 1.10
Protocol (for publication) Sprgeskema QOR 15 1
Recruitment arrangements (for publication) recruitment arrangements 1
Subject information and informed consent form (for publication) Deltagerinformation 5
Subject information and informed consent form (for publication) Dine rettigheder som forsgsperson i forsg med medicin 1
Summary of Product Characteristics (SmPC) (for publication) Fosfomycin SPC 1
Summary of Product Characteristics (SmPC) (for publication) Metronidazol SPC 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-06-13 Denmark Acceptable with conditions
2025-08-22
 2025-08-22
2 SUBSTANTIAL MODIFICATION SM-1 2025-08-25 Denmark Acceptable
2025-08-29
 2025-08-29
3 SUBSTANTIAL MODIFICATION SM-2 2025-10-24 Denmark Acceptable
2025-11-28
 2025-11-28
4 NON SUBSTANTIAL MODIFICATION NSM-1 2026-01-12 Denmark Acceptable
2025-11-28
 2026-01-12
5 NON SUBSTANTIAL MODIFICATION NSM-2 2026-01-12 Denmark Acceptable
2025-11-28
 2026-01-12
6 NON SUBSTANTIAL MODIFICATION NSM-3 2026-02-16 Denmark Acceptable
2025-11-28
 2026-02-16
7 NON SUBSTANTIAL MODIFICATION NSM-4 2026-02-19 Denmark Acceptable
2025-11-28
 2026-02-19
8 NON SUBSTANTIAL MODIFICATION NSM-5 2026-02-25 Denmark Acceptable
2025-11-28
 2026-02-25
9 NON SUBSTANTIAL MODIFICATION NSM-6 2026-03-19 Denmark Acceptable
2025-11-28
 2026-03-19
10 NON SUBSTANTIAL MODIFICATION NSM-7 2026-03-19 Denmark Acceptable
2025-11-28
 2026-03-19

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