Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202402557039838 Date of Approval: 02/02/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title LADEX (LAssa fever adjunct treatment with DEXamethasone)
Official scientific title Safety and tolerability of adjunct dexamethasone in addition to standard of care antiviral therapy compared to standard of care antiviral therapy alone for the treatment of moderate to severe Lassa Fever: An open label randomized controlled phase II clinical trial
Brief summary describing the background and objectives of the trial Lassa fever (LF) is a severe and often fatal systemic disease in humans. It is caused by the Lassa virus (LASV). Vaccines are not available yet and treatment options are limited to supportive care and ribavirin. Recent LF outbreaks in Nigeria showed an exceptionally high and increasing incidence of LF cases LF affects a large number of countries in West Africa. The pathophysiology of LF is not fully understood yet. It is hypothesized that the damage mediated by the host's defence is plays a key role in the pathophysiology of severe LF. Dexamethasone is considered to dampen the overactive immune response in a range of infectious diseases and thus preventing consecutive damage mediated by the host's immune system, while the anti-infective therapy is effectively treating the underlying pathogen. At the Irrua Specialist Teaching Hospital (ISTH) in Nigeria, one of the largest treatment centres for LF in West-Africa, dexamethasone has been successfully used in clinical practice to manage co-infections of LASV and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The primary objective is to assess safety and tolerability of dexamethasone in moderate to severe LF when administered as adjunct treatment. Secondary objectives are to assess the effect of the study intervention on disease progression; to assess immunological and virological impact of dexamethasone therapy and the characterization of population pharmacokinetic characteristics for patients treated with adjunct dexamethasone therapy.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LADEX
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Lassa fever
Purpose of the trial Treatment: Drugs
Anticipated trial start date 22/01/2024
Actual trial start date 05/02/2024
Anticipated date of last follow up 30/11/2026
Actual Last follow-up date 31/12/2026
Anticipated target sample size (number of participants) 42
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Standard of care plus dexamethasone Standard of care antiviral ribavirin therapy plus dexamethasone once daily 10 days Application of medicinal products i.v. Analysis of blood draws following a dedicated schedule included in the protocol. 21
Control Group Standard of care Standard of care antiviral ribavirin therapy 10 days Application of medicinal products i.v. Analysis of blood draws following a dedicated schedule included in the protocol. 21 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Age ≥ 18 years - LF confirmed by RT-PCR with a Ct value < 30 - Signs of significant health impairment as evidenced by any of the following: o ACVPU other than A o Systolic blood pressure < 90 mmHg o Seizure(s), meningism, coma, focal neurological deficit o AST (GOT) >3xULN o ALT (GPT) > 3xULN o KDIGO 2 or more severe based on serum creatinine only (where preceding value of creatinine is not available, the upper limit of the normal range should be used as reference) o Active macroscopic bleeding o O2 saturation < 92 - Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential) - Lactation following live birth - Known intolerance and contra-indications to ribavirin or dexamethasone - Patients who already received a corticosteroid within the preceding 7 days - Investigator’s valuation that patient might be put to substantial risk by participating in this trial - Patients receiving end-of-life care as judged by the investigator 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 120 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 12/12/2023 ISTH REC
Ethics Committee Address
Street address City Postal code Country
KM 87, Benin Auchi Road Irrua P.M.B8 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Proportion of treatment emergent adverse events and treatment emergent serious adverse events. Daily during the treatment of 10 days
Secondary Outcome a) Safety and tolerability of ribavirin in moderate to severe LF b) Unfavourable outcome (composite endpoint: AKI, ARDS, shock or encephalopathy or death) c) Mean/median decline and AUC of AST, ALT, CK, LDH and CRP d) Description of proinflammatory plasma cytokine levels (e.g. IFNα, TNFα, IL-6, IL-8) and lymphocyte phenotype under treatment e) Description of evolution of viral loads and infectious titres over time until day 10. f) Evolution of selected virus gene sequences under treatment g) Population pharmacokinetics of ribavirin and dexamethasone h) Time between treatment start and hospital discharge i) Length of IMC/ICU stay j) All-cause mortality on day of discharge According to dedicated time schedule included in the protocol over the 10 days treatment time.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Irrua Specialist Teaching Hospital KM 87, Benin Auchi Road Irrua P.M.B. 8 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Bernhard Nocht Institute for Tropical Medicine Bernhard-Nocht-Str. 74 Hamburg 20359 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Bernhard Nocht Institute for Tropical Medicine Bernhard-Nocht-Str. 74 Hamburg 20359 Germany Public institute
COLLABORATORS
Name Street address City Postal code Country
Hamburg University. Institute of Pharmacy. Research group Clinical Pharmacy Bundesstr. 45 Hamburg 20146 Germany
Irrua Specialist Teaching Hospital KM 87, Benin Auchi Road Irrua P.M.B. 8 Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Sylvanus A. Okogbenin okogbenins@yahoo.com +2348060476179 KM 87, Benin Auchi Road
City Postal code Country Position/Affiliation
Irrua P.M.B. 8 Nigeria Physician
Role Name Email Phone Street address
Scientific Enquiries Mirjam Groger groger@bnitm.de +4940285380550 Bernhard-Nocht-Str. 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany Physician
Role Name Email Phone Street address
Public Enquiries Cyril Erameh cyrilerameh@gmail.com +2348032413382 KM 87, Benin Auchi Road
City Postal code Country Position/Affiliation
Irrua P.M.B. 08 Nigeria Physician
Role Name Email Phone Street address
Public Enquiries Mirjam Groger groger@bnitm.de +4940285380550 Bernhard-Nocht-Str. 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany Physician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes In line with the funding conditions, IPD is to be shared. However, this will be de-identified IPD that used to generate the results reported (text, tables, figures and appendices). IPD sharing will begin after publication of primary results and will be available for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. The IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom IPD are made available will be required to be part of the execution of a data use agreement. Clinical Study Report,Informed Consent Form,Study Protocol From the time of publication and for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. Respective IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The data shall be made available through a governed data access process which includes a transparent, accountability and decision-making process: Completion of data request form. Evaluation by a data access committee. Data sharing agreement. Secure transfer of data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information