Comparison of the efficacy of inhaled heparin/N-acetylcysteine, N-acetylcystein alone, and placepo for the treatment of COVID-19 patients admitted to the hospital

Comparison of the efficacy of inhaled heparin/N-acetylcysteine, N-acetylcystein alone, and placepo for the treatment of COVID-19 patients

Three-arm double-blind phase-III randomized controlled trial with parallel groups with allocation concealment on 75 patients, using sealed envelopes for randomization

Patients with confirmed COVID-19 based on the PCR test admitted to the ICU of Payambar Azam Hospital, Bandar Abbas, Iran from March 11 to April 4, 2022 will be included according to the inclusion and exclusion criteria. This study is a double-blind randomized controlled trial so that neither the patients nor the investigator will be aware of the groupings. Patients will be randomly allocated to 3 groups (n=25) using sealed envelopes: The first group will receive the protocol treatments and 2 ml heparin from a 5000 IU vial (DarouPakhsh Co., Iran) plus 3 ml of NAC 20% (DarouPakhsh Co., Iran) amounting to an overall 5-ml nebulizer solution. The second group will receive 3 ml of NAC 20% plus 2 ml of distilled water and the third group 5 ml of distilled water. All groups will receive these treatments every 4 hours every day for 7 days.

Incision criteria: Definitive diagnosis of COVID-19 based on the results of the PCR test Admission to the intensive care unit Exclusion criteria: Hypersensitivity to heparin and N-acetyl cysteine Coagulopathies

The first group, the protocol treatments plus 2 ml heparin from a 5000 IU vial plus 3 ml of NAC 20% amounting to an overall 5-ml nebulized solution every 4 hours every day for 7 days The second group, the protocol treatments plus 3 ml of NAC 20% plus 2 ml of distilled water every 4 hours every day for 7 days The third group, the protocol treatments plus 5 ml of distilled water every 4 hours every day for 7 days.

Duration of ICU stay

Simple randomization with individuals as units of randomization along with allocation concealment: 75 unclear envelopes and 75 cards with the names of the groups (A, B, C) will be prepared (25 cards for each group). The cards will be put into the envelopes and the envelopes will be sealed and provided to the investigator. Upon entrance of each patient to the study, the envelopes will be shuffled and one will randomly be selected. The patient will be allocated to group A, B, or C based on the card inside the selected envelope.

A total of 5-ml vials will be prepared by an individual not involved in the study. Each 25 vials will be prepared based on the instructions for any of the three study groups. Then, a label indicating A, B, or C will be attached to each vial. The vials will be kept in an appropriated place and the investigator, the participants, the nurses responsible for drug administration, and all other individuals involved in the study will be unaware of the content of vials.