The Effect of Doxapram Versus Theophylline on Diaphragmatic Function

• ClinicalTrials.gov Identifier: NCT03894189
• Recruitment Status: Unknown
• First Posted: March 28, 2019
• Last Update Posted: March 28, 2019
• Sponsor: Beni-Suef University
• Information provided by (Responsible Party): Samaa Rashwan, Beni-Suef University

Study Description

Brief Summary:

Doxapram is licensed for drug-induced post-anesthesia respiratory depression , arousal effect and return airway protective reflexes caused by barbiturates, volatile anesthetics, nitrous oxide or benzodiazepines over dosage.

Value of theophylline to stimulate the respiratory neuronal network has been examined by previous studies and increases the activity of respiratory muscles, including the intercostal , transversus abdominis muscles and the diaphragm, it also has bronchodilator and anti-inflammatory effects.

Condition or disease	Intervention/treatment	Phase
Weaning Failure	Drug: Doxapram Hydrochloride; Drug: Theophylline	Not Applicable

Detailed Description:

This randomized comparative study will be conducted in the post-surgical cardio-thoracic intensive care unit in Beni -Suef University Hospital after approval of the department of anesthesiology, surgical ICU and pain management , and cardio thoracic department and the local ethics and research committee, and obtaining written informed consents from the patients to compare the effect of doxapram versus theophylline on diaphragmatic function using ultrasonography parameter: thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration] during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: The Effect of Doxapram Versus Theophylline on Diaphragmatic Function and Weaning From Mechanical Ventilation After Open Heart Surgery
• Estimated Study Start Date: May 2019
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: doxapram group (GROUP D); The patients in this group will receive loading dose of (1 mg/kg) followed by an infusion of (1mg/kg/h)	Drug: Doxapram Hydrochloride; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug; Other Name: Doxapram; Drug: Theophylline; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug
Active Comparator: theophylline group (GROUP T); the therapeutic loading dose (5mg/kg) followed by an infusion of (0.5 mg/kg/h)	Drug: Doxapram Hydrochloride; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug; Other Name: Doxapram; Drug: Theophylline; the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug

Outcome Measures

Primary Outcome Measures :

1. the effect of doxapram versus theophylline on diaphragmatic function [ Time Frame: the study drugs will be infused for 1 hour,At the end of 60 min of SBT, the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. ]
   : thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration](18) (19) during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: Patients (males and females) in the age group 20 -60 scheduled for elective open heart surgery ( e.g. coronary artery bypass grafting, valve replacement ) under cardiopulmonary bypass .

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Exclusion Criteria:The preoperative exclusion criteria:

1. Age older than 60 years
2. Preoperative left ventricular ejection fraction less than 30%
3. Chronic obstructive pulmonary disease
4. Significant hepatic disease (alanine aminotransferase or aspartate aminotransferase >150 U/l).
5. Renal failure (creatinine >200 μm).
6. History of seizure, or stroke.
7. History of diaphragmatic palsy, cervical spine injury, or neuromuscular disease (eg, myasthenia gravis, Guillain-Barré syndrome).
8. Lesion adjacent to the diaphragm
9. Intra-abdominal hypertension (intra-abdominal pressure ≥12 mm Hg )
10. Known allergy to the study drugs.

The Post enrollment exclusion criteria:

1. Postoperative hemorrhage (chest tube drainage ≥ 200 ml/h).
2. Surgical complications necessitating reoperation.
3. Postoperative cardiac failure necessitating high-dose inotropes or intra -aortic balloon pump.
4. Refractory hypoxemia (ratio of arterial oxygen tension [PaO2] to fraction of inspired oxygen [FIO2] <150 mmHg).
5. Occurrence of neurologic deficit.
6. -Myocardial ischemia (ST-segment depression) lasting more than 30 min

7. Failure of spontaneous breathing trial.

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Contacts and Locations

Contacts

Contact: Samaa ak Rashwan, MD; 020120159125; samakassemrashwan@gmail.com

Locations

Egypt

Beni-Suef University Hospital; Recruiting

Banī Suwayf, Egypt

Contact: Samaa Rashwan, MD 0201270159125

Sponsors and Collaborators

Beni-Suef University

Investigators

• Principal Investigator: Samaa ak Rashwan, MD; Assisstant proffesor of anesthesia

More Information

• Responsible Party: Samaa Rashwan, Samaa Abou Alkassem Rashwan, Beni-Suef University
• ClinicalTrials.gov Identifier: NCT03894189
• Other Study ID Numbers: Faculty Of Medicine,Beni -Suef
• First Posted: March 28, 2019
• Last Update Posted: March 28, 2019
• Last Verified: March 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Theophylline; Doxapram; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Purinergic P1 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Central Nervous System Stimulants