NOPE Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

4 Feb 2025 → ongoing

Decision date (initial)

2024-12-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ludwig Boltzmann Society

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To assess whether treatment with norfloxacin leads to a decrease in portal hypertension (PH) as evaluated by hepatic venous pressure gradient (HVPG) after 12 weeks in patients with decompensated cirrhosis (dACLD).

Secondary objectives 4

1. To assess whether norfloxacin treatment reduces the incidence of liver-related adverse events (i.e. infections, jaundice, ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, acute-on-chronic liver failure: ACLF) and liver-related death in comparison to a control group receiving placebo.
2. To assess whether norfloxacin treatment leads to a reduction of bacterial translocation (BT) and systemic inflammation (SI).
3. To assess the effect of norfloxacin on the microbiome composition and the blood metabolome.
4. To assess the effect of norfloxacin on patient-reported outcomes in patients with dACLD.

Conditions and MedDRA coding

Portal hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patients with dACLD undergoing liver vein catheterization for measurement of hepatic venous pressure gradient
2. Age 18-80 years
3. Written informed consent to participate in the study

Exclusion criteria 14

1. Lack of ability to give consent or unwillingness to participate in the study
2. Initiation of hepatitis C virus (HCV) or hepatitis B virus (HBV) treatment within the last year
3. Non-cirrhotic portal hypertension (e.g. PSVD)
4. Malignant diseases including hepatocellular carcinoma (HCC) at enrollment
5. Immunosuppression
6. Untreated/uncontrolled HIV infection
7. Long-term administration of antibiotic medication at study enrollment
8. Allergy to norfloxacin or other quinolones
9. Risk of incompliance/lack of adherence to the study protocol (at the investigator’s discretion)
10. Pregnancy or unwillingness to utilize effective means of contraception for the duration of the study in women of childbearing potential
11. QTc >480 ms at study screening
12. Serum creatinine >1.5 mg/dL at study screening or chronic hemodialysis
13. Bilirubin >5 mg/dL at study screening
14. High paracentesis frequency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in HVPG at 12 weeks compared to baseline in the treatment group as compared to placebo

Secondary endpoints 6

1. Incidence of liver-related complications at 12 weeks and at 24 weeks (Spontaneous bacterial peritonitis, Hepatorenal syndrome, Variceal bleeding, Jaundice, Large-volume ascites, Overt hepatic encephalopathy, Any other major infection (pneumonia, sepsis…), Acute-on-chronic liver failure (ACLF), Liver-related death)
2. Liver-related mortality
3. Biomarkers of bacterial translocation and systemic inflammation at 12 weeks (on-drug) and at 24 weeks (off-drug)
4. Patient-reported outcomes/HRQoL (using validated questionnaires: SF-36 v2.0, CLDQ, FSS) at 12 weeks (on-drug) and at 24 weeks (off-drug)
5. Stool microbiome composition at baseline vs. week 12
6. Blood metabolomic signatures at baseline vs. week 12

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Medicine III

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Medicine III

Locations

1 EU/EEA country · 1 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 12 files

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

Application history

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