Randomized multi-country adaptive phase IIb platform trial evaluating treatments for Crimean-Congo haemorrhagic fever (UMIT-2 Trial)
| ISRCTN | ISRCTN12205320 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12205320 |
| ClinicalTrials.gov (NCT) | NCT06860334 |
| Sponsor | Liverpool School of Tropical Medicine |
| Funder | Medical Research Council |
- Submission date
- 05/03/2026
- Registration date
- 11/03/2026
- Last edited
- 11/03/2026
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Crimean-Congo haemorrhagic fever (CCHF) is a serious viral infection that can spread between people and often causes severe illness or death. In some outbreaks, between 5% and 40% of people with the disease die, especially where medical care is limited. Most recent cases have occurred in Türkiye and Iraq, and the infection is now considered an important emerging global health threat.
There are currently no medicines proven to treat CCHF, and care mainly focuses on supporting patients — for example, by treating symptoms and managing complications.
The UMIT-2 trial (UMIT means “hope” in Turkish) is the first large study to test whether antiviral medicines can help people recover from CCHF. The study will take place in several hospitals in Türkiye and Iraq between 2026 and 2028.
Who can participate?
Adult inpatients (≥18 years) hospitalised with laboratory-confirmed CHFV infection.
What does the study involve?
Participants who agree to take part will be randomly placed into one of three groups:
• Standard care alone
• Favipiravir
• Ribavirin
Treatment will last about one week while the participant is in the hospital, and they will then be followed up for around one month.
These medicines aim to help the body remove the virus more quickly, as people with the most severe disease often have higher levels of the virus in their blood for longer. The UMIT-2 trial uses an adaptive design, which means that treatment groups can be stopped early if they do not work, or new treatments can be added as more evidence becomes available. If new treatments are added in the future, these will only be introduced after review and approval by ethics committees and regulatory authorities.
What are the possible benefits and risks of participating?
The results from UMIT-2 will help doctors and scientists understand which antiviral medicines are most effective against CCHF, improve treatment for patients, and guide future research into this dangerous disease.
Taking part in the UMIT-2 clinical trial does not present specific disadvantages beyond the potential side effects of the study medicines and the time commitment required for follow-up visits, including the Day 28 assessment. All medicines can cause side effects, although not everyone will experience them. Participant safety will be closely monitored throughout the study with regular clinical assessments and blood tests. Favipiravir is generally well tolerated but may cause mild gastrointestinal symptoms (such as nausea, vomiting, diarrhoea, or stomach pain), headache, dizziness, skin rash, or temporary changes in liver function tests or uric acid levels. Ribavirin has been used for many years to treat viral infections but can sometimes cause anaemia (a reduction in red blood cells), which may lead to tiredness or shortness of breath, as well as nausea, vomiting, reduced appetite, fever, chills, headache, muscle pain, or mood changes such as anxiety or irritability. Study procedures are similar to those used in routine hospital care for CCHF and include blood tests, physical examinations, monitoring of vital signs, throat or nose swabs, and reviews of medicines and symptoms. These procedures may cause brief discomfort, minor bruising from blood sampling, or short-lasting irritation from swabs. Study treatment may be stopped if it is considered not beneficial or not safe to continue.
Where is the study run from?
Liverpool School of Tropical Medicine, UK.
When is the study starting and how long is it expected to run for?
May 2026 to December 2027
Who is funding the study?
Medical Research Council (MRC), UK.
Who is the main contact?
umit@lstmed.ac.uk
Contact information
Public
Global Health Trials Unit
Department of Clinical Sciences
Liverpool School of Tropical Medicine
Room W-1-038, 1st Floor
Wolfson Building
Pembroke Place
Liverpool
L3 5PH
United Kingdom
| Phone | +441517053176 |
|---|---|
| umit@lstmed.ac.uk |
Scientific, Principal investigator
Global Health Trials Unit, LSTM
Department of Clinical Sciences
Room W-1-038, 1st Floor
Wolfson Building
Pembroke Place
Liverpool
L3 5PH
United Kingdom
 ORCID ID |
0000-0002-3712-415X |
|---|---|
| Phone | +44 151 705 3730 |
| tom.fletcher@lstmed.ac.uk |
Principal investigator, Scientific
Cumhuriyet University, Medical Faculty, Dept. of Infectious Diseases, Sivas, Türkiye
Sivas
58140
Türkiye
| Phone | +90 0346 258 000 |
|---|---|
| nelaldi@cumhuriyet.edu.tr |
Study information
| Primary study design | Interventional | |
|---|---|---|
| Allocation | Randomized controlled trial | |
| Masking | Open (masking not used) | |
| Control | Active | |
| Assignment | Parallel | |
| Purpose | Treatment | |
| Scientific title | UMIT-2: a randomized, multi-country, adaptive phase iib platform trial to determine the efficacy and safety of therapeutics for crimean-congo haemorrhagic fever | |
| Study acronym | UMIT-2 | |
| Study objectives | Primary Objectives: To compare CCHFV viral dynamics of investigational therapeutics relative to the control arm Secondary Objectives: To determine the safety and tolerability of investigational therapeutics relative to the control arm To compare time to successful hospital discharge between participants receiving investigational therapeutics, relative to the control arm To evaluate antiviral efficacy of investigational therapeutics To compare the overall mortality in patients with CCHF who receive different investigational therapeutics with those who receive the control arm To compare mortality rates among patients whose baseline predictors of disease place them in different categories for disease severity, who receive different investigational therapeutics. To characterise the plasma pharmacokinetics (PK) of therapeutics in CCHF Exploratory Objectives: To characterise virus, host immune response and viral resistance over time | |
| Ethics approval(s) |
1. Submitted 05/03/2026, Liverpool School of Tropical Medicine: Research Ethics Committee (LSTM REC, W-2-037, 1st Floor, Wolfson Building, LSTM, Pembroke Place, Liverpool, L3 5PH, United Kingdom; +44 151 702 9587; lstmrec@lstmed.ac.uk), ref: 25-013 2. Approved 05/03/2026, Samsun Ondokuz Mayis University Ethical Committee (Körfez, Ondokuz Mayıs Ünv, 55270 Atakum/Samsun, Samsum, 55270, Türkiye; +90 31211919; samsunkaek@omu.edu.tr), ref: KAD-FR-42 | |
| Health condition(s) or problem(s) studied | Adult in-patients (≥18 years) hospitalised with laboratory confirmed CHFV infection by positive polymerase chain reaction (PCR) test. | |
| Intervention | Description of randomisation: Participants will be randomised in a 1:1:1 ratio to one of three initial trial arms: standard of care, investigational antiviral A, or investigational antiviral B. Randomisation will be stratified by country to account for potential geographic differences in disease presentation, healthcare delivery, or standard treatment practices. Arm A: Optimised Standard of Care Arm B: Favipiravir: 6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705 (Intravenous and oral tablet formulations). IV Favipiravir 2400mg BD on day 1, Day 2 IV Favipiravir 1200mg BD, Day 3-7 PO Favipiravir 1200mg BD Arm C: Ribavirin: 1-3,4-dihydroxy-5-1,2,4-triazole-3-carboxamide (tablet formulation). Ribavirin will be given at standard dosing: Day 1 PO Ribavirin 33mg/kg (load dose) then 16mg/kg QDS, Day 2 PO Ribavirin 16mg/kg QDS, Day 3-5 PO Ribavirin 16mg/kg QDS, Day 6 to 7 PO Ribavirin 8mg/kg TDS. | |
| Intervention type | Drug | |
| Phase | Phase II | |
| Drug / device / biological / vaccine name(s) | IV Favipiravir, Oral Favipiravir, Oral Ribavirin | |
| Primary outcome measure(s) |
| |
| Key secondary outcome measure(s) |
| |
| Completion date | 31/12/2027 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 378 |
| Key inclusion criteria | 1. Adult in-patients (≥18 years) at the time of screening. 2. Confirmed CCHF infection: Laboratory confirmed CCHF infection defined as positive polymerase chain reaction (PCR) test within 5 days prior to randomisation 3. Ability to provide informed consent signed by study patient or legally acceptable representative (for illiterate individuals). 4. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception. 5. Severity Grading System (SGS) for CCHF – Low/moderate risk. (Appendix 15) 6. Less than or equal to 7 days from onset of CCHF symptoms 7. Willingness to participate in the full protocol 8. Requirement to be hospitalised for treatment |
| Key exclusion criteria | 1. Severe renal impairment: Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration (eGFR) rate <30 mL/min/1.73 m2) 2. Pregnant or breast feeding 3. Anticipated transfer to another hospital which is not a study site within 72 hours 4. Known Allergy to any study medication 5. Patients participating in another clinical trial of an investigational medicinal product (CTIMP) within the last 30 days. 6. Known hypersensitivity or allergy to any component of the investigational medicinal product (IMP) or its excipients or documented previous intolerance or significant adverse reaction to the active IMP. 7. Participation in another clinical trial involving an investigational medicinal product (CTIMP) within 30 days or five half-lives of the prior IMP (whichever is longer). 8. Any condition or circumstance which, in the opinion of the Investigator, would place the participant at undue risk, compromise safety, or interfere with trial participation or interpretation of results. 9. Severity Grading System (SGS) for CCHF – High risk (Appendix 15) 10. Patients taking the drugs listed below within 30 days or 5 times the half-life (whichever is longer) of enrolment: 10.1. Pyrazinamide 10.2. Repaglinide 10.3. Theophylline 10.4. Famciclovir, Sulindac |
| Date of first enrolment | 01/05/2026 |
| Date of final enrolment | 30/09/2027 |
Locations
Countries of recruitment
- Iraq
- Türkiye
Study participating centres
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan |
Editorial Notes
05/03/2026: Study’s existence confirmed by the Ondokuz Mayıs University Faculty of Medicine Clinical Research Ethics Committee
