E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10047468 |
E.1.2 | Term | Viral lower respiratory tract infections |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the CATALYST Trial are to measure the change over time in the amount of oxygen being carried in the blood compared to the amount of oxygen being breathed in, in patients with COVID-19.
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E.2.2 | Secondary objectives of the trial |
We also want to look at: 1) How good is the treatment (and usual care) over time and whether this leads to an improvement in the patient's overall condition/ wellbeing 2) Clinical measures such as breathing rate, body temperature, how long you are in hospital for 3) Levels and changes in certain blood test results 4) Looking at how safe these treatments are by looking at their side effects treatments |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A tissue bank will be established at the University of Birmingham and University of Oxford. Samples will be stored for use in laboratory based research projects that will have been approved by a Research Ethics Committee. This research may include genetic analysis although it is difficult to predict exactly what research might be done at this present time. Samples sent to the University will be identified by the patients unique trial number only. All samples will be stored in accordance with the Human Tissue Act 2004. Consent for the Sample Collection Sub-study is optional.
Research samples will be taken at the time points indicated and will broadly be in line with the ISARIC protocol. If a sample cannot be collected for clinical or logistical reasons, then a comment added to the patient’s notes, but this does not need to be reported as a deviation.
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E.3 | Principal inclusion criteria |
1) Hospitalised adult (≥16 yrs) patients with a laboratory-confirmed diagnosis of SARS-CoV-2 pneumonia (confirmed by reverse transcription polymerase chain reaction [RT-PCR] assay and chest X-ray) 2) Oxygen saturation (SaO2) of ≤94% while breathing ambient air or a ratio of the partial pressure of Oxygen (PaO2) to the fraction of inspired oxygen (FiO2) (PaO2:FiO2) ≤ 300 mg Hg (≤40kPa)
Arm 2: Usual Care + Gemtuzumab Ozogamicin) Specific Inclusion Crieria The following criterion will apply until at least 3 patients have been allocated the IMP: 3) intubated and requiring mechanical ventilation |
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E.4 | Principal exclusion criteria |
1) Patient or legal representative refusal 2) Receiving palliative care with no active treatment 3) Known veno-occlusive disease 4) Chronic Obstructive Pulmonary Disease (known FEV1 < 50% predicted or ambulatory or long term oxygen therapy) 5) Neutrophil count < 2 x 10^9/l or White Blood Cell Count < 4.0 x 10^9/l 6) Current participation in another COVID-19 interventional trial 7) Known pregnancy or breastfeeding women 8) Women of child bearing potential who are unwilling to effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the duration of the trial and the maximum period specified in Table 2. 9) Non-vasectomised men, sexually active with women of child bearing potential, who are not willing to practise effective contraception (i.e. condom with spermicide) for the duration of the trial and the maximum period specified in Table 2. 10) Known HIV or chronic Hepatitis B or C infection 11) Known contraindications to any of the Investigational Medicinal Products 12) Concurrent immunosuppression with biological agents or prednisone dose > 20mg 13) History of haematopoietic stem cell transplant or solid organ transplant 14) Any other indication or medical history, that in the opinion of the local investigator means the patient is unsuitable for trial participation 15) Patients with tuberculosis or other severe infections such as (non-COVID19) sepsis, abscesses, and opportunistic infections requiring treatment 16) Patients with moderate or severe heart failure (NYHA class III/IV) 17) Any other indication or medical history, that in the opinion of the local investigator means the patient is unsuitable for trial participation
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E.5 End points |
E.5.1 | Primary end point(s) |
The ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2), measured from randomisation to day 14, hospital discharge, death. SpO2 and FiO2 (or inspired oxygen) are measured as part of routine clinical care at least 4 hourly in intensive care, and 4-6 hourly on the wards for patients receiving active management. The ratio will be derived from these data from the electronic patient record. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
measured from baseline to day 14 |
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E.5.2 | Secondary end point(s) |
• Efficacy measure (randomisation to day 7, 14 and 28) o Time to improvement; improvement defined as at least a one-point improvement on the Clinical Progression improvement Scale (1-10 scale; for the purposes of this trial level 0, no viral RNA detected, will not be assessed) [WHO R&D Blueprint Group]. o Clinical Progression Scale [WHO R&D Blueprint Group] at randomisation, day 7, 14 and 28 • Clinical measures o Respiratory rate o Body Temperature o Length of hospital stay o Hospital survival status at day 28 o Proportion of patients discharged at day 28 o Destination of discharge • Routine laboratory measurment (baseline, days 1, 3, 7 and 14) o C-reactive protein (CRP) o Full blood count with neutrophil:lymphocyte ratios o Ferritin, D-Dimer, LDH and triglycerides • Safety measures o Adverse events as recorded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 (Appendix 1 )of grade ≥3 with interest in veno- occlusive disease, secondary infection and allergic reaction. o Survival status
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Varies dependent on endpoints - time points are indicated for each one above |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial is designed to be amended subsequently with new treatment arms in the future for up to a maximum of three years. The end of trial will be six months after the last patient’s last data capture. This will allow sufficient time for the completion of protocol procedures, data collection and data input. The Trials Office will notify the MHRA and main REC that the trial has ended and will provide them with a summary of the clinical trial report within 12 months of the end of trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 6 |