Clinical trial NCT04920838: Early Treatment of Vulnerable Individuals With Non-Severe SARS-CoV-2 Infection
Official title: Early Treatment of Vulnerable Individuals With Non-Severe SARS-CoV-2 Infection: A Multi-Arm Multi-Stage Randomized Trial (MAMS) to Evaluate the Effectiveness of Several Specific Treatments in Reducing the Risk of Clinical Worsening or Death in Sub-Saharan Africa (COVERAGE-Africa)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Covid19
Covid19 Drug Treatment
Severe Acute Respiratory Syndrome Coronavirus 2
SARS-CoV2 Infection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: University of Bordeaux
name: Institut National de la Santé Et de la Recherche Médicale, France
name: PACCI Program
name: Alliance for International Medical Action
name: Centre Muraz
name: Barcelona Institute for Global Health
First posted: 2021-06-10
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicentre, multiple country, randomised, open-label, adaptive, platform clinical study aiming to determine the efficacy and safety of various treatment regimens for prevention of the need for hospitalisation for specialised care due to severe progression of COVID-19.

The study is designed with the ability to incorporate the adding or dropping of treatment arms and that will include similar inclusion and non-inclusion criteria, the same primary and secondary endpoints, common data entry procedures, a shared database and a single statistical methodology for analysis of the primary endpoint.
Primary purpose: TREATMENT

Brief summary: Coverage Africa is a nested study in the large Anticov platform trial that aims to generate data on new early treatment strategies for mild/moderate COVID-19 patients in resource-limited-settings to reduce the number progressing to severe forms requiring hospitalization, thereby relieving the burden on health care systems and contributing to "flattening the curve" in contexts where none pharmaceutical intervention such as quarantine are difficult to implement in large urban settings. Treating early when the virus is still present might also limit transmission. Coverage Africa will be conducted in Guinea and Burkina Faso.

The main objective is to conduct an open-label, multicenter, randomized, adaptive platform trial to test the safety and efficacy of several marketed products, including antiviral therapies versus control in mild/moderate of coronavirus disease 2019 (Covid-19) in resource-limited-settings.

The study aims to recruit 600 patients in both countries, one site in Guinea and two sites in Burkina Faso.

The current assessed treatments are now the association of Fluoxétine/Budésonide compared with a control arm: paracetamol.

The adaptive design trial will allow for the removal of drugs, or the addition of new study arms when new data becomes available. Data on the primary efficacy parameters and safety will be integrated with the primary endpoint based on an oxygen saturation percentage (SpO2) ≤ 93% or death within 14 days after randomization to treatment, including death for any reason.

Study will run until August 2022. However, with the proposed adaptive design, the study could also be interrupted for success earlier than planned with the identification of a treatment that significantly reduces hospitalization rate as evidence by results from the primary endpoint.


Eligibility criteria: Inclusion Criteria:

* Adults 18 years of age at the time of screening or \>= 40 years and presenting at least one comorbidity : high blood pressure; a known obesity and/ or a known and treated diabete.
* SARS-CoV-2 infection confirmed by molecular biology (RT-PCR on a nasopharyngeal or oropharyngeal swab) or by antigen test validated in the country according to national guidelines
* A viral syndrome with or without uncomplicated pneumonia, defined as blood oxygen saturation level (SpO2) \>=94%.
* Mild Covid-19 symptoms with an onset \< 7 days before inclusion.
* Signed written consent from the patient or his/her representative.
* No need an oxygen therapy according to international guidelines (WHO Progression Scale, grade 2 to 4)
* Accepting and having the ability to be reached by telephone throughout the study.
* Having designated a contact person who can be contacted in case of emergency.
* Accepted to be reached by phone along throughout the study

Exclusion Criteria:

* Blood oxygen saturation level (SpO2) \< 94%.
* Known hypersensitivity to investigational products
* Chronic treatment with inhaled corticosteroids (up to 30 days)
* Known history of renal or hepatic failure
* Abnormal physical examination findings:

  * respiratory rate \< 25 per minute;
  * Clinical hypotension with associated signs justifying hospital care
* Feeling unwell for more than 7 days prior to screening.
* End-organ compromise requiring admission to a resuscitation or continuous care unit or short-term life-threatening comorbidity with life expectancy \< 3 months.
* For any new antiviral included in the study, prior treatment with the antiviral, presence of contraindication to its use or intake of concomitant medication proscribed with its use.
* Patients with known suicidal thoughts, severe psychiatric disorders or major depression that is uncontrolled or controlled by one of the prohibited drugs
* Known history of long QT syndrome or severe ventricular cardiac arrhythmia (ventricular tachycardia, patients with recovered ventricular fibrillation)
* Unwilling or unable to comply with the requirements of the study protocol at any time during the study, e.g. no access to or not comfortable with use of a smartphone or with answering questions using a telephone, in the opinion of the Investigator or cannot use an inhalation chamber.
* Any other reason that makes it impossible to monitor the patient during the study.
* Enrolled in other clinical trials with unregistered drugs or with registered drugs that may interact with any of the study IPs or are contraindicated as concomitant therapy within the last 3 months prior to screening

Primary outcomes:
measure: SpO2 ≤ 93% within 14 days
timeFrame: From inclusion (day 0) to day 14.
measure: Death within 14 days
timeFrame: From inclusion (day 0) to day 14.
Secondary outcomes:
measure: Death within 28 days
timeFrame: From inclusion (day 0) to day 28.
measure: Occurence of at least one grade 3 or 4 clinical or biological adverse event within 14 days
timeFrame: From inclusion (day 0) to day 14.
measure: Number of hospitalizations due to severe progression
timeFrame: From inclusion (day 0) to day 28.
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: Centre Muraz/INSP
city: Conakry
country: Guinea
facility: Centre de traitement des maladies à tendance épidémique de Gbessia
Study officials:
References: