Non-invasive Ventilation in Reducing the Need for Intubation in Patients With Cancer and Respiratory Failure

A Prospective Randomized Controlled Trial of Early Non-Invasive Positive Pressure Ventilation in Patients With Hypoxemic Respiratory Failure and Malignancies

This randomized clinical trial studies how well non-invasive ventilation works in reducing the need for intubation, or placement of a tube in the windpipe, in patients with cancer and respiratory failure. Respiratory failure is a condition in which not enough oxygen passes from the lungs to the blood, and is a common cause of admission to the emergency room in patients with hematological and solid tumor patients. Non-invasive positive pressure ventilation (NIPPV) is a method of delivering oxygen using a mask. It is not yet known whether NIPPV is better at improving the amount of oxygen in the blood, reducing shortness of breath, and the need for intubation than standard high flow oxygen (a tube with 2 prongs placed in the nostrils) in patients with cancer and respiratory failure.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm
• Intervention / Treatment: Drug: Methylprednisolone; Device: Positive Air Pressure Device; Procedure: Oxygen Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the percent of patients who meet criteria for intubation within 28 days of study inclusion.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A (NIPPV THERAPY): Patients undergo intermittent NIPPV, with the recommended schedule comprising 2 hours on NIPPV followed by =< 2 hours off NIPPV and continuous NIPPV at night or while sleeping for 8 hours per day, for 28 days or until discharged from the hospital.

ARM B (HIGH FLOW OXYGEN THERAPY): Patients continue to receive high flow nasal cannula oxygen therapy using current protocol for titration of high flow oxygen therapy for 28 days or until discharged from the hospital. Patients may receive NIPPV if they develop evidence of accessory muscle use with breathing or at the discretion of the treating physician.

IDIOPATHIC PULMONARY SYNDROME (IPS) SUBGROUP (INCLUDING DIFFUSE ALVEOLAR HEMORRHAGE): Patients with IPS receive methylprednisolone daily on days 0-48 and every other day (QOD) on days 49-55 in parallel with NIPPV or oxygen therapy, with a taper at the discretion of the treating physician.

After completion of study, patients are followed up until day 100.

• Study Type: Interventional
• Enrollment (Estimated): 256
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nisha Rathi, MD; Phone Number: 713-792-5040; Email: NRathi@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Nisha Rathi; Phone Number: 713-792-5040; Email: NRathi@mdanderson.org
      • Principal Investigator: Nisha Rathi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio =< 300 mmHg OR a peripheral capillary oxygen saturation (SaO2):FiO2 =< 357
• Have a diagnosed malignancy
• Chest radiograph or computed tomography (CT) scan within =< 3 months prior to study enrollment rules out primary or metastatic malignancy in the lungs or pleural space as a significant cause of respiratory insufficiency
• Probability of survival is at least 6 months

Exclusion Criteria:

• Presence of do not resuscitate (DNR)/do not intubate (DNI) orders at study entry
• Clinical evidence of left heart failure as the main etiology for respiratory compromise
• Evidence of active intrathoracic malignancy (primary or metastatic) in the lungs or pleural space that is a significant cause of respiratory insufficiency
• Patients with acute chronic obstructive disease exacerbation as the primary etiology for respiratory failure
• Evidence of accessory respiratory muscle use with breathing
• Shock (need for vasopressor therapy or mean arterial pressure [MAP] < 60 despite fluid administration)
• Oliguric acute renal failure (urine output < 500 ml/day) unless already on hemodialysis
• Patient already on NIPPV at the time of screening
• pH < 7.30 or partial pressure of carbon dioxide (pCO2) > 50 (if available)
• Fixed upper airway obstruction
• Airway or facial trauma that would hinder the use of a NIPPV mask
• Uncontrolled tachy or bradyarrhythmia or active myocardial ischemia defined as either: atrial fibrillation with rapid ventricular response (heart rate [HR] > 120 beats per minute [bpm]), ventricular tachycardia or nonsustained ventricular tachycardia (any rate), supraventricular tachycardia (any rate), third degree heart block (any rate), heart rate less than 40 beats per minute (regardless of the rhythm)
• Active myocardial ischemia defined as a clinical presentation at the time of screening consistent with acute coronary syndrome which includes unstable angina and electrocardiogram (EKG) changes suggestive of an either an acute ST elevation myocardial infarction (new ST elevations or new left bundle branch block) or acute non-ST elevation myocardial infarction (new ST depressions, new T wave inversions)
• Glasgow Coma Scale (GCS) < 8 or inadequate airway protective reflexes
• Undrained pneumothorax/pneumomediastinum
• Copious secretions (> 20 cc's of sputum production per hour or significant hemoptysis defined as > 100 cc's of hemoptysis in a 24 hour period
• Risk for gastric aspiration (ie; ileus, esophageal or bowel obstruction, active vomiting)
• Recent esophageal, gastric or bowel surgery (within 3 weeks of study enrollment)
• Inability to cooperate with NIPPV
• Refusal to receive NIPPV
• Respiratory arrest

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (NIPPV therapy); Patients undergo intermittent NIPPV, with the recommended schedule comprising 2 hours on NIPPV followed by =< 2 hours off NIPPV and continuous NIPPV at night or while sleeping for 8 hours per day, for 28 days or until discharged from the hospital.	Drug: Methylprednisolone; IPS cohort only; Other Names: Medrol; Wyacort; Adlone; Caberdelta M; DepMedalone; Depo Moderin; Depo-Nisolone; Duralone; Emmetipi; Esametone; Firmacort; Medlone 21; Medrate; Medrol Veriderm; Medrone; Mega-Star; Meprolone; Methylprednisolonum; Metilbetasone Solubile; Metrocort; Metypresol; Metysolon; Predni-M-Tablinen; Prednilen; Radilem; Sieropresol; Solpredone; Summicort; Urbason; Veriderm Medrol; Device: Positive Air Pressure Device; Undergo NIPPV
Active Comparator: Arm B (high flow oxygen therapy); Patients continue to receive high flow nasal cannula oxygen therapy using current protocol for titration of high flow oxygen therapy for 28 days or until discharged from the hospital. Patients may receive NIPPV if they develop evidence of accessory muscle use with breathing or at the discretion of the treating physician.	Drug: Methylprednisolone; IPS cohort only; Other Names: Medrol; Wyacort; Adlone; Caberdelta M; DepMedalone; Depo Moderin; Depo-Nisolone; Duralone; Emmetipi; Esametone; Firmacort; Medlone 21; Medrate; Medrol Veriderm; Medrone; Mega-Star; Meprolone; Methylprednisolonum; Metilbetasone Solubile; Metrocort; Metypresol; Metysolon; Predni-M-Tablinen; Prednilen; Radilem; Sieropresol; Solpredone; Summicort; Urbason; Veriderm Medrol; Procedure: Oxygen Therapy; Receive high flow oxygen therapy; Other Names: supplemental oxygen therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of patients who require intubation or meet criteria for intubation	Fisher's exact test or a chi-squared test will be used to assess the association between two categorical variables. The intubation rate by 28 days and 95% confidence intervals will be estimated for each treatment arm. Logistic regression will be utilized to assess the effect of patient prognostic factors on the intubation rate by 28 days.	Up to 28 days from study inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to intubation	The Kaplan-Meier method will be used to estimate the time-to-event distribution for each treatment group, and the median time will be provided. The log-rank test will be used to examine the time-to-event distribution of the active treatment group versus that of the control. Time to intubation rate at different time points will be provided by treatment group (i.e. at 7 days, 14 days, 21 days, and 28 days). Since there might be other competing risks for intubation, a competing risk analysis will be performed treating these early events as a competing event for intubation.	Up to 28 days
Intensive care unit length of stay	Descriptive statistics, including the mean, standard deviation, median, and range, will be provided. The t-test or Wilcoxon's rank sum test will be used to evaluate the difference between the non-invasive positive pressure ventilation (NIPPV) arm and the control arm.	Up to 28 days
Hospital length of stay	Descriptive statistics, including the mean, standard deviation, median, and range, will be provided. The t-test or Wilcoxon's rank sum test will be used to evaluate the difference between the NIPPV arm and the control arm.	Up to 28 days
Change in partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio	Descriptive statistics, including the mean, standard deviation, median, and range, will be provided. The t-test or Wilcoxon's rank sum test will be used to evaluate the difference between the NIPPV arm and the control arm.	Baseline up to 28 days

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Nisha Rathi, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2015
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimated): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Neoplasms; Respiratory Insufficiency; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: 2015-0165 (Other Identifier: M D Anderson Cancer Center); NCI-2015-01514 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No