Adaptive RCT of Corticosteroids for Severe Adenovirus Pneumonia in Adults (CAPSTONE-AD)

Qingyuan Zhan

Status and phase: Not yet enrolling; Phase 3

Conditions: Adenovirus Infections, Human

Treatments: Drug: low dose Methylprednisolone; Drug: Moderate dose Methylprednisolone; Drug: Saline (0.9%, sterile, for infusion)

Study type: Interventional

Funder types: Other

Identifiers

NCT07152600

2025-I2M-C&T-B-090A

Details and patient eligibility

About

Severe community-acquired pneumonia caused by adenovirus (hereafter referred to as severe adenovirus pneumonia) is one of the common forms of severe community-acquired pneumonia in immunocompetent adults. It predominantly affects young individuals, progresses rapidly, and is associated with a high incidence of respiratory failure and multiple organ dysfunction. At present, there is no effective antiviral therapy available in China, and the reported mortality rate ranges from 41.5% to 80%. How to effectively reduce the mortality of severe adenovirus pneumonia, on the basis of conventional supportive care, is crucial for improving the prognosis of critically ill patients and alleviating the burden on families and society. We are currently conducting an adaptive, randomized, open-label controlled trial aimed at reducing mortality in severe adenovirus pneumonia. The primary objective of this study is to evaluate the efficacy and safety of adjunctive corticosteroid therapy at different dosages, in addition to early standard supportive treatment, in lowering mortality among patients with severe adenovirus pneumonia.

Enrollment: 262 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years.

• Admission to the Intensive Care Unit (ICU).

• Meeting the diagnostic criteria for community-acquired pneumonia (CAP).

• Meeting at least one of the major diagnostic criteria for severe pneumonia:

  (i) Requirement for endotracheal intubation and mechanical ventilation;

(ii) Septic shock requiring vasopressor therapy after adequate fluid resuscitation.

-Or simultaneously fulfilling three of the minor criteria:

(i) Respiratory rate ≥ 30 breaths/min;

(ii) PaO₂/FiO₂ ≤ 250 mmHg;

(iii) Multilobar infiltrates;

(iv) Altered mental status and/or disorientation;

(v) Blood urea nitrogen ≥ 20 mg/dL (7.12 mmol/L);

(vi) Leukopenia (white blood cell count < 4 × 10⁹/L);

(vii) Thrombocytopenia (platelet count < 100 × 10⁹/L);

(viii) Hypothermia (core temperature < 36 °C);

(ix) Hypotension (systolic blood pressure < 90 mmHg) requiring aggressive fluid resuscitation.

• Confirmed adenovirus etiology: at least one positive nucleic acid test (PCR) or next-generation sequencing (NGS) result for adenovirus in respiratory specimens (respiratory secretions, throat swabs, or bronchoalveolar lavage fluid).
• Severe community-acquired pneumonia (SCAP) patients admitted to the emergency department/ward/ICU due to respiratory failure within < 72 hours.
• Signed informed consent.

Exclusion criteria

• Patients receiving vasopressor therapy for septic shock at the time of enrollment.
• Terminally ill patients (expected survival <30 days, e.g., advanced malignancy).
• Clinical history suggesting overt aspiration.
• Documented active gastrointestinal bleeding.
• Presence of cystic fibrosis, obstructive pneumonia, active influenza, pulmonary tuberculosis, or fungal infection.
• Active viral hepatitis or active herpesvirus infection.
• Bone marrow suppression or HIV infection.
• Refusal of mechanical ventilation and endotracheal intubation.
• Uncontrolled hyperglycemia (diabetic ketoacidosis with blood ketones >3 mmol/L, or hyperosmolar hyperglycemic state with blood glucose >33.3 mmol/L and elevated osmolality).
• Known allergy to corticosteroids.
• Patients requiring anti-inflammatory corticosteroids or replacement hydrocortisone for any reason, or those already receiving prednisone >15 mg/day (or equivalent dose of another corticosteroid).
• Pregnant or breastfeeding women.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

262 participants in 3 patient groups, including a placebo group

Standard of Care

Placebo Comparator group

Description:

Control group

Treatment:

Drug: Saline (0.9%, sterile, for infusion)

Low dose steroids

Experimental group

Description:

treated with low dose corticosteroids

Treatment:

Drug: low dose Methylprednisolone

Moderate dose steroids

Experimental group

Description:

treated with moderate dose corticosteroids

Treatment:

Drug: Moderate dose Methylprednisolone