The plea comes after it was revealed that none of the ECIs so far submitted by the public have resulted in new legislation.
A total of 56 citizen initiatives have been submitted since the launch of the scheme in 2012. Of these, only three succeeded in getting the required one million signatures but none of them had a single result.
In a bid to relaunch the initiative, 20 April was designated 'ECI Day' and new measures are planned to help raise awareness of it.
A campaign group is now calling on the Commission to intensify efforts to rescue the ECI.
Cologne-based Democracy International has gathered a petition with 76,397 signatures it will send to the Parliament demanding a "stronger ECI."
The European Citizens' Initiative was launched officially on 26 January 2012. The initiative gives citizens a way to propose legislation on matters where the EU has competence to legislate, such as environment, agriculture, transport and public health.
Citizens must form a committee composed of at least seven EU citizens being resident in at least seven different member states. A citizens' initiative must be backed by at least one million EU citizens, coming from at least seven out of the 27 member states.
A spokesman for Democracy International told this website, "At the end of 2015 we were promised a victory for the citizens of Europe.
"Parliament voted in absolute majority for a powerful ECI to give people real political influence in the EU but since then nothing has happened.
"Given the dangerous spread of populism and anti-European rhetoric right across Europe, it is all the more crucial that the EU builds its democratic legitimacy and gives a stronger voice to its citizens."
It has written to the Commission President Jean-Claude Juncker, his special advisor on citizens Luc Van Den Brande, and Frans Timmermans, the Dutch Commissioner responsible for the ECI.
The Democracy International spokesman said, "We told them that they need to act fast in order to keep the citizens on board, and that they must grasp this last chance to save the ECI from irrelevance.
"Given the gradual erosion of Europe, EU politicians must not shirk from their responsibility to do everything in their powers to defend European democracy.
"The European Citizens' Initiative could give people a voice in the EU, but in its current form it is unusable and powerless. We want the Commission to take up our proposals on how to save the ECI.
"More Europeans need to be informed about their right; it must be made easier to start ECIs and successful initiatives must have a true political impact."
On Wednesday, the future of the ECI was discussed at a conference organised by the European Economic and Social Committee (EESC).
Its Vice President Michael Smyth said, "ECI is an instrument for citizens to take a role in European policy making but after five years of experience we see it is not working properly. It is time for the European Commission to act."
"Providing citizens with an effectively working instrument to voice their needs and concerns could have a tangible influence on European politics making it more targeted, relevant and in particular more democratic."
"How reliable is an EU which introduces an instrument for a more democratic and more participatory union in its treaty and then doesn't care whether it's working or not? Four years without a single result or follow up on an ECI, should be a wake up-call for the Commission."
Many of the participants from civil society organizations voiced similar concerns at the ECI Day, saying they were not only "disappointed" that the Commission postponed the review of the ECI but also that Timmermans was not present to join in the debate.
Other EU institutions have voiced concern, including the European ombudsman, who has drawn up 11 guidelines for an improvement of the ECI while the Parliament has sent a resolution with "clear and specific" proposals for a revised ECI.
The Committee of the Regions (CoR), meanwhile, has adopted an opinion calling for a "rapid and substantial" revision of the ECI.
The ombudsman Emily O'Reilly said, "What citizens and I want to know is the real honest thinking of the Commission about the ECI."
She urged the Commission to "finally explain what citizens ultimately can expect to achieve."
Antonio Longo, the rapporteur of the EESC's opinion on the ECI, said the poor take up was "not only a setback for European people but also for the democratic values of the EU.
"In times where trust in the EU institutions decreases and coherence within Europe loosens, it is more than important to give Europeans the feeling that their concerns matter. With an easy to handle and functioning ECI-instrument the EU can regain both reliability and authority. It's high time for the Commission to react."
The Commission in its report of April 2015 recognised that organisers of the ECI face "many difficulties" and confirmed that it has postponed the review of the scheme.