## Protocol Section
### Identification Module
**NCT ID:** NCT04649879

**Brief Title:** Convalescent Plasma for Treatment of COVID-19

**Official Title:** Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial

#### Organization Study ID Info
**ID:** CP3
#### Organization
**Class:** OTHER
**Full Name:** Karolinska University Hospital
### Status Module
#### Completion Date
**Date:** 2022-01-26

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-02-09

**Type:** ACTUAL

**Last Update Submit Date:** 2022-01-26

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-01-26

**Type:** ACTUAL

#### Start Date
**Date:** 2020-12-03

**Type:** ACTUAL

**Status Verified Date:** 2022-01

#### Study First Post Date
**Date:** 2020-12-02
**Type:** ACTUAL
**Study First Submit Date:** 2020-12-01
**Study First Submit QC Date:** 2020-12-01
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Karolinska Institutet

**Class:** OTHER

**Name:** Danderyd Hospital

**Class:** OTHER

**Name:** Falu Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** Joakim Dillner

#### Responsible Party

**Investigator Affiliation:** Karolinska University Hospital

**Investigator Full Name:** Joakim Dillner

**Investigator Title:** Professor of Infectious Disease Epidemiology; Director of R&D

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Convalescent plasma has been shown to be safe and effective for treatment of several diseases. Preliminary data indicate that it is safe for treatment of COVID-19. We found that viremia upon admission identifies patients at 7 fold increased risk of admission to intensive care and 8 fold increased risk of death. CP treatment appeared to result in rapid viral clearance in a small case series. CP appeared to be well tolerated in a phase I study in which patients only received one dose of CP and a phase II study in which CP was given until viremia disappeared (unpublished data).

Randomised controlled studies assessing the efficacy of CP are lacking and thus the efficacy of CP is unknown. Preliminary data indicate that treatment should be given early, prior to development of severe illness. Detection of viremia upon admission identifies a group at high risk of severe disease and death that has the most to benefit from CP. Phase II study data indicates that treatment should be given until SARS-CoV-2 is no longer detected in serum and the donor antibody neutralization titres should be ≥1/640. A randomised controlled trial in which viremic patients are treated with CP with the equivalent of an antibody titre ≥1/640 is thus required to determine if CP can be an effective COVID-19 treatment.

### Conditions Module

**Conditions:**

- Covid19

**Keywords:**

- COVID-19 convalescent plasma treatment

- SARS-CoV-2 infection

- Viremia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Patients will be randomised 2:1 to treatment with convalescent plasma and standard of care only. Randomisation is by random permutated blocks using Redcap or equivalent.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 59

**Type:** ACTUAL

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** * Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions.
* If steroid therapy has not already been initiated, betamethasone 3 mg daily will be given concomitantly with steroid therapy or longer if clinically indicated but for a maximum of 10 days.

**Intervention Names:**

- Biological: SARS-CoV-2 convalescent plasma

**Label:** Convalescent plasma treatment

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Standard of care for COVID-19 patients.

**Intervention Names:**

- Other: Standard of care

**Label:** Control

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Convalescent plasma treatment

**Description:** Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions. CP will be given as a slow infusion over 2 hours. CP neutralization titre of ≥ 1/640 or an ELISA reactivity against the Spike protein of SARS-CoV-2 by the Euroimmun commercial assay \>9 is desired. New antibody tests are under development and can be used instead if equivalence to neutralization or Euroimmun ELISA is demonstrated.

**Name:** SARS-CoV-2 convalescent plasma

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Control

**Description:** Standard of care as determined by hospital practices for COVID-19 patients.

**Name:** Standard of care

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Death of a study participant within 28 days.

**Measure:** COVID-19 related mortality within 28 days

**Time Frame:** Measured 28 days after inclusion into the study.

#### Secondary Outcomes

**Description:** Death of a study participant within 60 days.

**Measure:** COVID-19 related mortality within 60 days

**Time Frame:** Measured 60 days after inclusion into the study.

**Description:** * The need for mechanical ventilation and date when this was initiated
* For patients not eligible for intensive care: each day when PaO2/FiO2 ratio was less than 70 for ≥ 12 hours. PaO2 and FiO2 will be estimated from SO2% and O2 flow in nasal cannula, face mask or face mask with reservoir based on EPIC II data. A ratio of 70 is approximately equal to 90% SO2 with 8-9 L of Oxygen flow using a face mask with a reservoir.

**Measure:** Requirement of invasive ventilation or Pao2/FiO2 ≤ 70 for ≥ 12 hours in the case of patients not eligible for intensive care

**Time Frame:** Until discharged from the hospital, up to 2 months

**Description:** Possible adverse events will be elicited using a modification and Swedish translation (appendix 6) of Common Terminology Criteria for Adverse Events v5.0 and they will be continuously reported to the sponsor. Adverse events related to convalescent plasma therapy shall be followed to assess reversibility.

**Measure:** Adverse events

**Time Frame:** The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.

**Description:** Measured as doses of convalescent plasma administered (1-10 infusions, 200ml).

**Measure:** Dose of plasma needed to clear viremia

**Time Frame:** 28 days

**Description:** Blood samples for detection of SARS-CoV-2 in the blood will be taken prior to treatment start, daily during treatment and until two consecutive negative results are obtained.

**Measure:** Time to clearance of viremia

**Time Frame:** Until discharged from the hospital, up to 2 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age greater than or equal to 18
* Admitted to a study hospital
* Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples and blood
* Negative pregnancy test taken before inclusion and use of an acceptable effective method of contraception until treatment discontinuation if the participant is a woman of childbearing potential
* Written informed consent after meeting with a study physician and ability and willingness to complete follow up

Exclusion Criteria:

* No matching plasma donor (Exact matching in the ABO system is required)
* Unavailability of plasma
* Estimated glomerular filtration rate \<30 (kidney failure stage III or more)
* Pregnancy (urinary-hcg)
* Breast feeding
* Inability to give informed consent

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Falun

**Country:** Sweden

**Facility:** Department of Infectious Disease, Falu Hospital

**State:** Dalarn

**Zip:** 79182

**Location 2:**

**City:** Stockholm

**Country:** Sweden

**Facility:** Department of Geriatrics, Karolinska University Hospital

**Zip:** 171 76

**Location 3:**

**City:** Stockholm

**Country:** Sweden

**Facility:** Danderyd Hospital

**Zip:** 18257

### IPD Sharing Statement Module

**Description:** The investigators will be sharing the data, but the management plan is being designed.

**Info Types:**

- STUDY_PROTOCOL

**IPD Sharing:** YES

### References Module

#### References

**Citation:** Dillner J, Ursing J. Convalescent plasma for treatment of COVID-19: study protocol for an open randomised controlled trial in Sweden. BMJ Open. 2021 Dec 8;11(12):e048337. doi: 10.1136/bmjopen-2020-048337.

**PMID:** 34880010

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000011024

- Term: Pneumonia, Viral

- ID: D000011014

- Term: Pneumonia

- ID: D000012141

- Term: Respiratory Tract Infections

- ID: D000007239

- Term: Infections

- ID: D000014777

- Term: Virus Diseases

- ID: D000018352

- Term: Coronavirus Infections

- ID: D000003333

- Term: Coronaviridae Infections

- ID: D000030341

- Term: Nidovirales Infections

- ID: D000012327

- Term: RNA Virus Infections

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M2561

- Name: COVID-19

- Relevance: HIGH

- As Found: COVID-19

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17511

- Name: Viremia

- Relevance: LOW

- As Found: Unknown

- ID: M13904

- Name: Pneumonia

- Relevance: LOW

- As Found: Unknown

- ID: M13914

- Name: Pneumonia, Viral

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M20490

- Name: Coronavirus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6555

- Name: Coronaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M23685

- Name: Nidovirales Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15149

- Name: RNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000086382

- Term: COVID-19

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: Resp

- Name: Respiratory System Agents

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

- ID: M4909

- Name: Betamethasone

- Relevance: LOW

- As Found: Unknown

- ID: M12147

- Name: Myeloma Proteins

- Relevance: LOW

- As Found: Unknown

- ID: M13179

- Name: Paraproteins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
