Randomized, Controlled, Open, Multicentric Clinical Trial to Evaluate the Efficacy and Safety of a Combination of Anti-Tuberculous Drugs Based on High Dose Rifampicin, High Dose Moxifloxacin and Linezolid in Patients with Bacilliferous Pulmonary Tuberculosis (Rml-Tb).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

17 Jan 2024 → 10 Apr 2025

Decision date (initial)

2023-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509075-17-00

EudraCT number

2021-001626-22

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy and safety of a regimen based on high-dose rifampicin, high-dose moxifloxacin and linezolid for 8 weeks versus standard treatment in patients with smear-positive pulmonary tuberculosis.

Secondary objectives 1

1. 1. To evaluate the tolerability (any adverse events) of the experimental arm vs. standard treatment arm. 2. Evaluate the dynamics of efficacy as a decrease in bacterial load as a function of time and increase in time until sputum positivity. 3. To analyze the correlation between the AUC/MIC of rifampicin, moxifloxacin and linezolid with the “result” of efficacy. 4. Assess quality of life using specific questionnaires (SF-12 and St George respiratory questionnaire among study participants) 5. Carry out a cost-effectiveness study to explore the viability of the implementation of the experimental arm in the National Health System.

Conditions and MedDRA coding

Bacilliferous pulmonary tuberculosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Age >18 years 2. Diagnosis of smear-positive pulmonary tuberculosis 3. Signature of consent form 4. Negative pregnancy test in women of childbearing age (defined as a woman who has had menarche and has not yet had menopause, with the exception of infertile women, which includes, among other situations, women with a hysterectomy, women with a double salpingectomy and women with double oophorectomy).

Exclusion criteria 1

1. 1. Recent contact with a patient with multidrug-resistant tuberculosis 2. Multidrug-resistant tuberculosis or monoresistance to any of the first-line drugs (except ethambutol) 3. Positive smear microscopy with negative mycobacterial culture. 4. Barthel <60 or the investigator considers that there is a risk of poor prognosis in the following months 5. Weight less than 40kg 6. Treatment with drugs that can prolong QT in the last month before randomization for more than 7 days (azithromycin, chloroquine, chlorpromazine, cisapride, clarithromycide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxine, thioridazine, amiodarone). 7. Cirrhosis Child C 8. User of drugs of abuse according to the researcher's criteria 9. Patient with solid organ or bone marrow transplant. 10. Patient on treatment with anti-TNF or other immunosuppressive drugs 11. Patients with oncohematological diseases Advanced lung disease according to the researcher 13. Epilepsy or non-stable psychiatric illness. 14. History of ischemic coronary heart disease or severe arrhythmia in the previous 6 months 15. Long QT syndrome or family history of sudden death 16. Patient with HIV diagnosis 17. Women who breastfeed 18. Allergy or intolerance to any of the study drugs 19. History of TB in the previous year 20. Any of the following laboratory alterations: AST or ALT > 3 times the upper limit of normal b Total Bi > 3 times the upper limit of normal c Hb< 6.5 g/dl d Platelets < 40,000/mm^3 e Potassium < 3.2 mmol/L f GFR<30 ml/min/1.73m^2 21. Any of the following alterations in the ECG: at QTcF>0.5sec b Other clinically relevant changes in the ECG according to the investigator. 22. Treatment with any of the drugs included in the trial for more than 7 days in the last month. 23. Participants who are being treated with serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5HT1 receptor agonists (triptans), direct or indirect acting sympathomimetics (including adrenergic bronchodilators, pseudoephedrine and phenylpropanolamine), vasopressors (e.g. epinephrine, norepinephrine), dopaminergic medications (e.g. dopamine, dobutamine), pethidine or buspirone and cannot be removed or replaced by drugs of another class at the discretion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy: Proportion of patients with sterilization of sputum culture in liquid medium 8 weeks after starting treatment Safety: Proportion of patients with grade 3 or higher adverse events according to CTCAE V5.

Secondary endpoints 1

1. To evaluate the tolerability of the experimental arm at 8 weeks after randomization. To evaluate the dynamics of efficacy of the experimental arm vs. control arm using the decrease in time until positive culture and time until sputum becomes negative.Analyze the correlation between the PK parameters To evaluate the quality of life of the patients. Carry out a cost-effectiveness study.To analyze the immunological and inflammatory pattern of the study participants

Investigational products

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

Test 4

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Sponsor organisation

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Address

Passeig De La Vall D'Hebron 119-129

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Contact name

Angélica Valderrama Rodríguez

Public contact point

Organisation

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Contact name

Angélica Valderrama Rodríguez

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Summary of results Art. 37(4) CTR

Documents 8 files

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

Application history

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