iNO300 Therapy in Critically Ill Patients With Pneumonia
Purpose
The goal of this clinical trial is to learn the formation and recovery rate of methemoglobin (MetHb) in severely sick patients with pneumonia who receive high doses of inhaled nitric oxide (iNO) therapy at 250 parts per million (ppm), not exceeding 300 ppm. Meanwhile, the benefits of the therapy to treat severely sick patients with pneumonia will be explored. Patients who are 18 years or older, newly diagnosed with pneumonia, and severely sick with requirement of a breathing machine could be included. The main questions it aims to answer are: How does methemoglobin change through the iNO treatment? Does iNO therapy increase the number of patients recovering from pneumonia? Researchers will compare iNO treatment to placebo, which means using the same device as the treatment group without delivering the study drug. Participants will: - Receive iNO treatment starting at 250 ppm, not exceeding 300 ppm, 40 min, every 6 hours, from day 1 to day 5 - Be followed up for 60 days
Conditions
- Critical Illness
- Pneumonia
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 18 years or older - Intubated and mechanically ventilated - Within 72h of diagnosis of community- or hospital-acquired pneumonia - Written informed consent obtained from patients or legally authorized representatives
Exclusion Criteria
- Baseline methemoglobin 3% or higher - Genetic diseases including glucose-6-phosphate dehydrogenase deficiency, cytochrome b5 reductase deficiency, sickle cell disease - Oxygen saturation < 88% on 100% inspired fraction of oxygen - Anemia with hemoglobin < 7.0 g/dl - Acute cardiogenic shock requiring inotropic or mechanical support with an ejection fraction less than 20% - eGFR < 30 ml/min/1.73m2 or use of continuous renal replacement therapy - Receiving inhaled NO therapy or decision to initiate inhaled NO therapy within 24 hours post randomization - A decision to do-not-resuscitate (DNR) - Enrollment in another experimental antimicrobial treatment protocol - Patients for whom follow-up is expected to be impossible
Study Design
- Phase
- Early Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental iNO300 group |
High dose inhaled nitric oxide starting at 250 ppm (not exceeding 300 ppm) , 40min, 4 times daily, from day 1 to day 5. Nitric oxide is delivered using a gas cylinder containing nitric oxide and nitrogen. |
|
|
Sham Comparator Control group |
Sham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Massachusetts General Hospital
Detailed Description
This study is designed as a pilot, double-blinded, randomized controlled trial to investigate levels of methemoglobin in the treatment group versus the control group and efficacy of high dose inhaled NO among critically ill patients with pneumonia. We will enroll 34 adult patients with newly diagnosed pneumonia and invasive mechanical ventilation who are admitted to the ICUs at Massachusetts General Hospital. After enrollment, participants will be randomized in 1:1 ratio to intervention group or control group. Baseline characteristics will be collected. During treatment period, patients allocated to the intervention group will receive high dose inhaled NO starting at 250 ppm (not exceeding 300 ppm), 40min, 4 times daily, for 5 days. The control group will receive sham intervention. Both groups will receive standard therapy. During follow-up period, we will follow participants for a total duration of 60 days. Methemoglobin kinetic levels and efficacy outcomes will be collected.