Anti-Coronavirus Therapies–Inpatient - ACT–Inpatient

Aug 29, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Canadian Institutes for Health Research, Bayer AG, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation.
Date Presented:
08/29/2022
Date Published:
08/29/2022
Date Updated:
08/29/2022
Original Posted Date:
08/29/2022
References

Contribution To Literature:

Among inpatients with COVID-19 in the ACT–Inpatient trial, the addition of colchicine or low-dose rivaroxaban + aspirin had no benefit compared with control for mortality or need for high flow oxygen or ventilation.

Description:

The goal of the trial was to assess the safety and efficacy of colchicine, rivaroxaban, and aspirin among inpatients with coronavirus disease 2019 (COVID-19).

Study Design

Patients were randomized in a 2 x 2 factorial fashion to either colchicine (n = 1,304) vs. control (n = 1,307), or rivaroxaban plus aspirin (n = 1,063) or control (n = 1,056). Colchicine was given as 1.2 mg followed by 0.6 mg 2 hours later, then 0.6 mg twice daily for 28 days. Rivaroxaban was given as 2.5 mg BID for 28 days and aspirin as 100 mg daily for 28 days.

  • Total number of enrollees: 2,611 (colchicine vs. control); 2,119 (rivaroxaban + aspirin vs. control)
  • Duration of follow-up: 45 days
  • Mean patient age: 56 years
  • Percentage female: 42%

Inclusion criteria:

  • Symptomatic and laboratory-confirmed diagnosis of COVID-19
  • Age ≥18 years
  • Within 72 hours (ideally 24 hours) of admission or worsening clinically

Exclusion criteria:

  • Advanced kidney or liver disease
  • Pregnancy (known or potential) or lactation
  • Already ventilated for >72 hours
  • Allergy or planned use of study interventions or taking drugs that are contraindicated in combination

Other salient features/characteristics:

  • Fully vaccinated: 11%
  • Days of symptoms: 7 days
  • Oxygen at baseline: 80%
  • Intensive care unit: 12%

Principal Findings:

The primary outcome, high flow oxygen, ventilation, death, for colchicine vs. control was: 28.2% vs. 27.2% (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.90-1.21, p = 0.58).

  • Death: 20.2% vs. 19.1% (p = 0.38)
  • High flow oxygen or ventilation: 18.9% vs. 19.3% (p = 0.84)

The primary outcome, major thrombosis, high flow oxygen, ventilation, death, for rivaroxaban + aspirin vs. control was: 26.4% vs. 28.4% (p = 0.32).

  • Death: 18.2% vs. 17.6% (p = 0.66)

Secondary outcomes for rivaroxaban + aspirin vs. control:

  • Any bleeding: 1.6% vs. 0.7% (p = 0.04)

Interpretation:

The results of this trial indicate that among inpatients with COVID-19, the addition of colchicine or low-dose rivaroxaban + aspirin had no benefit compared with control for mortality or need for high flow oxygen or ventilation. One limitation is that no placebo was used in this trial and the overall mortality was quite high (~20%). Results for the colchicine arm are consistent with other trials showing a null effect on hard endpoints among COVID-19 patients. The addition of anticoagulation may reduce VTE events, but is balanced by a higher risk of bleeding.

References:

Presented by Dr. Sanjit Jolly at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 29, 2022.

Eikelboom J, Rangarajan S, Jolly SS, et al. The Anti-Coronavirus Therapies (ACT) Trials: Design, Baseline Characteristics, and Challenges. CJC Open 2022;4:568-76.

Clinical Topics: Anticoagulation Management, COVID-19 Hub, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Aspirin, Colchicine, COVID-19, ESC22, ESC Congress, Inpatients, Intensive Care Units, Oxygen, Primary Prevention, Rivaroxaban, Thrombosis, Venous Thromboembolism, Ventilators, Mechanical


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