Back to results

mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R) (TACTIC-R)

Primary Purpose

COVID19

Status

Unknown status

Phase

Phase 4

Locations

United Kingdom

Study Type

Interventional

Intervention

Ravulizumab

Baricitinib

Standard of care

About this trial

This is an interventional treatment trial for COVID19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

To be included in the trial the participant must:

Be aged 18 and over
Have clinical picture strongly suggestive of COVID-19-related (with/without positive COVID-19 test) AND
- Risk count (as defined below) >3 OR
- ≥ 3 if risk count includes "Radiographic severity score >3"
Be considered an appropriate subject for intervention with immunomodulatory in the opinion of the supervising clinician
Be able to be maintained on venous thromboembolism prophylaxis or current maintenance therapy during inpatient dosing period, according to local guidelines

Exclusion Criteria

The presence of any of the following will preclude participant inclusion:

Inability to supply direct informed consent or assent from Next of Kin or Independent Healthcare Provider on behalf of patient
Mechanical ventilation at time of prior to dosing
Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients
Currently on any of the study investigational medicinal products
Known unresolved Neisseria meningitidis infection
Unwilling to be vaccinated against Neisseria meningitidis or receive prophylactic antibiotic cover until 2 weeks after vaccination
Known active tuberculosis (no blood screening required)
Known active Hepatitis B or C (no blood screening required); active varicella zoster
Concurrent participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed)
Patient moribund at presentation or screening
Pregnancy at screening (or unwillingness to adhere to pregnancy advice in protocol)
Unwillingness to adhere to breastfeeding advice in protocol
Either alanine transaminase or aspartate transaminase (ALT or AST) > 5 times the upper limit of normal
Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance < 30 ml /min/1.73 m^2)
Currently receiving probenecid or chronic IVIG treatment
Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern.

Risk Count

Patients will be given a Risk Count equal to the cumulative points received for the following criteria (no = 0 points, yes = 1 point):

Male gender, Age > 40 years, Non-white ethnicity, Diabetes, Hypertension, Neutrophils > 8.0x10^9/L, CRP > 40mg/L, Radiographic severity score >3

Sites / Locations

Cambridge University Hospitals NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Standard of care

Ravulizumab + Standard of care

Baricitinib + Standard of care

Arm Description

Standard of care

Ravulizumab IV (adjusted to weight, Day 1 only)

Baricitinib PO OD (4mg, Days 1-14)

Outcomes

Primary Outcome Measures

Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure

Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73m^2), haemofiltration or dialysis

Secondary Outcome Measures

Change in clinical status as assessed on 7-point ordinal scale compared to baseline

The clinical status of the patients is assessed using 7-point ordinal scale as follows: 1 = Death, 2 = Mechanical ventilation, 3 = Non-invasive or high flow oxygen, 4 = Low flow oxygen, 5 = Hospitalised - no oxygen, 6 = Discharged - normal activities not resumed, 7 = Discharged - normal activities resumed

Proportion of patients with adverse events of special interest in each treatment arm

The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: venous thromboembolism, new infections requiring antimicrobials

Time to Sp02 >94% on room air

The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days

Time to first negative SARS-CoV2 PCR

The amount of time between a patient's first positive SARS-CoV2 PCR test and a patient's first negative SARS-CoV2 PCR test, measured in days

Duration of oxygen therapy

The duration of oxygen therapy given to a patient, measured in days

Duration of hospitalisation

The duration of hospitalisation of a patient, measured in days

All cause mortality at day 28

The number of deaths recorded at 28 days irrespective of the cause

Time to clinical improvement

The time to clinical improvement for a patient, defined as: >2 point improvement from Day 1 on the 7-point ordinal scale, measured in days

Full Information

NCT ID

NCT04390464

First Posted

May 8, 2020

Last Updated

May 14, 2020

Sponsor

Cambridge University Hospitals NHS Foundation Trust

1. Study Identification

Unique Protocol Identification Number

NCT04390464

Brief Title

mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)

Acronym

TACTIC-R

Official Title

mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Unknown status

Study Start Date

May 8, 2020 (Actual)

Primary Completion Date

May 7, 2021 (Anticipated)

Study Completion Date

May 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cambridge University Hospitals NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

TACTIC-R is a randomised, parallel arm, open-label platform trial for investigating potential treatment for COVID-19 disease. While SARS-CoV infection evades detection by the immune system in the first 24 hours of infection, it ultimately produces a massive immune system response in the subgroup of people who develop severe complications. Most tissue damage following infection with COVID19 appears to be due to a later, exaggerated, host immune response. This leads to lung and sometimes multi-organ damage. Most people who develop these severe complications still have virus present in their respiratory tract at the time-point when the disease starts to evolve. Immune modulation in the presence of active infection has potential to cause more harm than benefit. Safety considerations when studying immune modulation strategies are paramount. Therefore, this study proposes to assess the efficacy of immunomodulatory agents that target dysregulated immune response that drive the severe lung, and other organ, damage. The medications investigated for efficacy in this trial are Baricitinib and Ravulizumab.

Detailed Description

TACTIC-R will assess the efficacy of the immunomodulatory agents Baricitinib and Ravulizumab as potential treatments for COVID-19 disease against Standard of Care alone. These agents target the dysregulated immune response that drives the severe lung, and other organ, damage frequently seen during COVID-19 infection. This trial will compare these immunomodulatory agents to Standard of Care over a 14-day treatment period, with follow-up at 28 and 90 days. Patients will be randomised in a 1:1:1 ratio across treatments. TACTIC-R will use a platform design with interim analysis to make efficient decisions about efficacy and futility (e.g. lack of efficacy and risk of harm) of the trial treatments. This enables the trial to stop recruiting to arms early where a clear efficacy decision can be made. It also allows for the addition of further arms. TACTIC-R will also iterate an algorithm for use of clinical and biochemical phenotyping to: Stratify patients to therapeutic arms according to probability of efficacy Identify early indicators of failure of therapeutic strategy. By collecting samples for genomics, transcriptomics, proteomics and immunological phenotyping, parallel studies associated with TACTIC-R will investigate host susceptibility factors for development of severe COVID-19-related disease and predictive biomarkers of response to therapeutic strategy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID19

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

TACTIC-R is a randomised, parallel arm, open-label platform trial.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1167 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Standard of care

Arm Type

Active Comparator

Arm Description

Standard of care

Arm Title

Ravulizumab + Standard of care

Arm Type

Experimental

Arm Description

Ravulizumab IV (adjusted to weight, Day 1 only)

Arm Title

Baricitinib + Standard of care

Arm Type

Experimental

Arm Description

Baricitinib PO OD (4mg, Days 1-14)

Intervention Type

Drug

Intervention Name(s)

Ravulizumab

Other Intervention Name(s)

Ultomiris

Intervention Description

Ravulizumab (Ultomiris, Alexion Pharmaceuticals) is a monoclonal antibody that binds to terminal complement protein C5 and prevents the complement-mediated destruction of cells. It is administered by intravenous infusion. Ravulizumab has a marketing authorisation in the UK for treating Paroxysmal Nocturnal Haemoglobinuria in adults.

Intervention Type

Drug

Intervention Name(s)

Baricitinib

Other Intervention Name(s)

Olumiant

Intervention Description

Baricitinib is administered orally once daily. It is licensed for treatment of rheumatoid arthritis, it is a relatively fast acting disease modifying anti-rheumatic drug and has the potential to be scaled up for use for a pandemic.

Intervention Type

Other

Intervention Name(s)

Standard of care

Intervention Description

Regular standard of care for COVID-19 patients

Primary Outcome Measure Information:

Title

Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure

Description

Time Frame

up to Day 14

Secondary Outcome Measure Information:

Title

Change in clinical status as assessed on 7-point ordinal scale compared to baseline

Description

Time Frame

14 days

Title

Proportion of patients with adverse events of special interest in each treatment arm

Description

The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: venous thromboembolism, new infections requiring antimicrobials

Time Frame

14 days

Title

Time to Sp02 >94% on room air

Description

The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days

Time Frame

14 days

Title

Time to first negative SARS-CoV2 PCR

Description

The amount of time between a patient's first positive SARS-CoV2 PCR test and a patient's first negative SARS-CoV2 PCR test, measured in days

Time Frame

14 days

Title

Duration of oxygen therapy

Description

The duration of oxygen therapy given to a patient, measured in days

Time Frame

14 days

Title

Duration of hospitalisation

Description

The duration of hospitalisation of a patient, measured in days

Time Frame

14 days

Title

All cause mortality at day 28

Description

The number of deaths recorded at 28 days irrespective of the cause

Time Frame

28 Days

Title

Time to clinical improvement

Description

The time to clinical improvement for a patient, defined as: >2 point improvement from Day 1 on the 7-point ordinal scale, measured in days

Time Frame

14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria To be included in the trial the participant must: Be aged 18 and over Have clinical picture strongly suggestive of COVID-19-related (with/without positive COVID-19 test) AND Risk count (as defined below) >3 OR ≥ 3 if risk count includes "Radiographic severity score >3" Be considered an appropriate subject for intervention with immunomodulatory in the opinion of the supervising clinician Be able to be maintained on venous thromboembolism prophylaxis or current maintenance therapy during inpatient dosing period, according to local guidelines Exclusion Criteria The presence of any of the following will preclude participant inclusion: Inability to supply direct informed consent or assent from Next of Kin or Independent Healthcare Provider on behalf of patient Mechanical ventilation at time of prior to dosing Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients Currently on any of the study investigational medicinal products Known unresolved Neisseria meningitidis infection Unwilling to be vaccinated against Neisseria meningitidis or receive prophylactic antibiotic cover until 2 weeks after vaccination Known active tuberculosis (no blood screening required) Known active Hepatitis B or C (no blood screening required); active varicella zoster Concurrent participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed) Patient moribund at presentation or screening Pregnancy at screening (or unwillingness to adhere to pregnancy advice in protocol) Unwillingness to adhere to breastfeeding advice in protocol Either alanine transaminase or aspartate transaminase (ALT or AST) > 5 times the upper limit of normal Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance < 30 ml /min/1.73 m^2) Currently receiving probenecid or chronic IVIG treatment Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern. Risk Count Patients will be given a Risk Count equal to the cumulative points received for the following criteria (no = 0 points, yes = 1 point): Male gender, Age > 40 years, Non-white ethnicity, Diabetes, Hypertension, Neutrophils > 8.0x10^9/L, CRP > 40mg/L, Radiographic severity score >3

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Elena Hernan-Sancho

Phone

01223 349132

Ext

349132

elena.hernansancho@addenbrookes.nhs.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frances Hall Hall, FRCP (UK), D.Phil

Organizational Affiliation

Cambridge University Hospitals NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cambridge University Hospitals NHS Foundation Trust

City

Cambridge

State/Province

Cambridgeshire

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Elena Hernan Sanch0

Phone

01223369824

elena.hernansancho@addenbrookes.nhs.uk

First Name & Middle Initial & Last Name & Degree

Maria King

Phone

07792173955

maria.king@addenbrookes.nhs.uk

12. IPD Sharing Statement

Citations:

PubMed Identifier

34473343

Citation

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Results Reference

derived

PubMed Identifier

32641154

Citation

Kulkarni S, Fisk M, Kostapanos M, Banham-Hall E, Bond S, Hernan-Sancho E, Norton S, Cheriyan J, Cope A, Galloway J, Hall F, Jayne D, Wilkinson IB. Repurposed immunomodulatory drugs for Covid-19 in pre-ICu patients - mulTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19 - Repurposed Drugs (TACTIC-R): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jul 8;21(1):626. doi: 10.1186/s13063-020-04535-4.

Results Reference

derived

Learn more about this trial

mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)

We'll reach out to this number within 24 hrs