Local Antibiotic Delivery for Community Acquired Pneumonia (LANDCAP 2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gentofte Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2024-07-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk Foundation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To examine whether treatment with inhaled levofloxacin 240 mg twice daily and no systemic antibiotics for 4-5 days is non-inferior as measured by days alive and out of hospital within 14 days compared to intravenous piperacillin/tazobactam.

Secondary objectives 6

1. To reduce proportion of patients with antibiotic side-effects
2. To preserve diversity in the gut microbiome following treatment
3. To examine whether inhaled levofloxacin is non-inferior on 30-day all-cause mortality.
4. To examine whether inhaled levofloxacin is non-inferior as measured by readmission, intensive care transfers or death within 30 days.
5. To examine whether inhaled levofloxacin is non-inferior on biochemical and vital parameters (blood pressure, tenperature, peripheral oxygen saturation)
6. To examine whether inhaled levofloxacin is non-inferior on patient-reported outcomes

Conditions and MedDRA coding

Community-acquired pneumonia

Study design 2 periods

Regulatory references

Plan to share IPD

No

IPD plan description

We do not plan to share individual participant data.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Hospital admission within 24 hours.
2. Radiologically new-onset chest infiltrate that is consistent with pneumonia and symptoms or signs also consistent with pneumonia, such as fever, cough, sputum, dyspnoea and/or chest pain.
3. The physician in charge of the patient’s treatment has decided that the patient should be treated with IV piperacillin/tazobactam.
4. C-reactive protein >50 OR central body temperature >38.0o C (1-3 of these fulfilled).
5. Age ≥ 18 years.
6. Able to give informed consent.

Exclusion criteria 14

1. Septic shock according to the sepsis III criteria; i.e., is organ dysfunction (defined as SOFA≥2) due to a dysregulated response to infection as well as persisting hypotension requiring vasopressors to maintain MAP≥65 mm Hg and serum lactate level>2 mmol/L (18 mg/dL) despite adequate volume resuscitation.
2. Oxygen requirement ≥5L/min to maintain 95% saturation.
3. Respiratory rate >24/min with relevant oxygen therapy.
4. Patient meets criteria for addition of macrolide to the antibiotic treatment.
5. Positive COVID or influenza test (PCR or antigen test).
6. Known allergy to levofloxacin or other fluoroquinolones or a serious adverse reaction when previously treated with a fluoroquinolone.
7. Prior tendinitis or tendon-rupture related to fluoroquinolone treatment.
8. Known allergy to β-lactam antibiotics.
9. Medical history of myasthenia gravis.
10. Reduced kidney function (eGFR < 20).
11. Expected transfer to ICU or death within 48 hours or a do not resuscitate ordination at time of recruitment.
12. Suspected aspiration pneumonia, pulmonary abscess, or pleural empyema / complicated parapneumonic effusion.
13. Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) > 480ms).
14. Pregnancy (a negative pregnancy test is required prior to inclusion of all pre-menopausal women).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Days alive and out of hospital at 14 days.

Secondary endpoints 12

1. Days alive and out of hospital at 30 days.
2. Days alive and out of hospital and without antibiotics at 30 days.
3. Proportion of patient with antibiotic-related side-effects
4. Differences in gut microbiome diversity and composition in stool and oral samples on day 5 and on day 60.
5. All-cause mortality at 30 days.
6. Proportion of patients converted to guideline-based therapy according to algorithm as described in the section titled “Procedures, patient monitoring and data collection”.
7. Proportion of patients readmitted, admitted to ICU or dead at 30 days.
8. CRP on day 5, continuous and binary (higher than on any day from 1 to 4 including baseline).
9. MAP ≤ 65 OR respiratory frequency > 25 OR pulse > 100 OR needing supplemental oxygen (1-4 of these fulfilled) on day 5.
10. PCT on day 5, continuous and binary (higher than on any day from 1 to 4 including baseline)
11. Temperature ≥ 38.0 on day 5.
12. Patient reported outcome measurements: Changes in Visual Analogue Scales for dyspnoea, cough, and fatigue from day 1 to day 5.

Investigational products

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

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gentofte Hospital

Sponsor organisation

Gentofte Hospital

Address

Gentofte Hospitalsvej 1

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Gentofte Hospital

Contact name

Jens Ulrik Stæhr Jensen

Public contact point

Organisation

Gentofte Hospital

Contact name

Jens Ulrik Stæhr Jensen

Third parties 1

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Application history

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