The Per-procedural Antibiotic Prophylaxis in Patients Undergoing Transcatheter Aortic Valve Implantation Trial (PAPPI)

The study is a prospective, crossover, cluster randomized trial in patients undergoing transcatheter aortic valve implantation (TAVI). The study tests whether cephalosporin plus beta-lactam antibiotic with spectrum for Enterococcus faecalis as per procedural prophylaxis is superior to cephalosporin alone in reducing the composite outcome of bacteremia or death at 6 months post-TAVI.

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Drug: Beta-lactam antibiotic with spectrum for Enterococcus faecalis; Drug: Cephalosporin

Detailed Description

The PAPPI trial is designed as a prospective, crossover, unblinded, cluster randomized trial. The study includes all TAVI centers in Denmark. Each center will be included for either single dose cephalosporin (1st, 2nd or 3rd generation) plus a beta-lactam antibiotic with spectrum for Enterococcus faecalis (e.g. ampicillin 2g) or single dose of a cephalosporin (1st, 2nd or 3rd generation) as antibiotic prophylaxis in relation to TAVI. The antibiotic(s) will be given as a single dose intravenously per-procedural. Patients will be followed from date of TAVI procedure until 6 months post procedure.

The primary outcome of the PAPPI trial will be a composite of the following components within 6 months post TAVI:

• Bacteremia (excluding all enterobacterales)
• Death

Secondary outcomes will be each separate component of the primary outcome and will be ana-lyzed separately as time-to-first event analysis. Additional secondary outcomes will be;

• Bacteremia (excluding all enterobacterales)
• Acute kidney failure
• Death
• Length of hospital stay
• Days-out-of-hospital from TAVI to 6 months

• Study Type: Interventional
• Enrollment (Estimated): 1986
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emil L Fosbøl, MD, PhD; Phone Number: + 45 35 45 63 40; Email: emil.fosboel@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Copenhagen University Hospital, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients > 18 years of age undergoing TAVI at sites in Denmark

Exclusion Criteria:

• Patients who do not want to participate and have chosen to "opt-out" of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cephalosporin (1st, 2nd or 3rd generation) + betalactam with spectrum for Enterococcus faecalis	Drug: Beta-lactam antibiotic with spectrum for Enterococcus faecalis; Beta-lactam antibiotic with spectrum for Enterococcus faecalis (e.g. ampicillin 2g) add-on in combination with cephalosporin as per-procedural prophylaxis in TAVI; Drug: Cephalosporin; Cephalosporin treatment
Active Comparator: Cephalosporin (1st, 2nd, 3rd generation)	Drug: Cephalosporin; Cephalosporin treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with a composite outcome of bacteremia or death by 6 months.	Bacteremia is defined as having positive blood cultures (excluding all enterobacterales) registered in the Danish Microbiological Database at 6 months post-TAVI. Death is defined as being registered as deceased in the Danish Civil Registration System at 6 months post-TAVI.	6 months post-TAVI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who died by 6 months	Death is defined as being registered as deceased in the Danish Civil Registration System 6 months post-TAVI.	6 months post-TAVI
Bacteremia assessed by collection of blood cultures.	Bacteremia is defined as having positive blood cultures (excluding all enterobacterales) registered in the Danish Microbiological Database at 6 months post-TAVI.	6 months post-TAVI
Number of patients with acute kidney failure assessed by plasma creatinine levels.	Acute kidney failure is defined as ≥50% increase in the plasma creatinine within 6 months post-TAVI and information on plasma creatinine levels is obtained from the national blood sample data.	6 months post-TAVI
Length of hospital stay	Length of hospital stay in relation to the TAVI-procedure	From the day of TAVI-procedure until the day of discharge after the TAVI-procedure e.g. days from TAVI-procedure until discharge assessed up to 6 months post-TAVI due to end of follow-up.
Days-out-of-hospital from TAVI to 6 months	Days-out-of-hospital from TAVI to 6 months	6 months post-TAVI

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Bacteremia; Aortic Valve Replacement; Aortic Valve Stenosis; Cephalosporin; Transcatheter Aortic Valve Replacement; Aortic Valve; Ampicllin; Per Procedure Prophylaxis
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Heart Valve Diseases; Ventricular Outflow Obstruction; Bacterial Infections; Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Aortic Valve Stenosis; Bacteremia; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; beta-Lactams; Lactams; Thiazines; Cephalosporins; Monobactams
• Other Study ID Numbers: p-2025-19665

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No